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Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space
Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space Part V: Phagocytosis and nuclear patterns of giant cells observed on the implanted lens surface K. Uenoyama, M.D., M. Tamura, M.D., C. Kinoshita, M.D., R. Kanagawa, M.D., S. Ohmi, M.D., T. Nakao, M.D., S. Saika, M.D.
ABSTRACT The major cellular components on intraoculal' lenses experimentally implanted in the .'abbit eye and in the mouse peritoneal space were examined. They consisted of macrophages and their metamorphosed epithelioid cells with occasional formations of fOl'eignbody giant cells from the fusion of the macrophage-related cells. Lymphocytes, individually and in clusters , were also seen on the lenses implanted in the mouse peritoneal space but l'arely on those implanted in the rabbit eye. Macrophages, epithelioid cells, and giant cells exhibited active phagocytosis on the implanted intraocular lenses. These cells phagocytized not only minor foreign particles such as artificially fed latex 0., carbon colloids but also living cells including e.'ythrocytes, leukocytes, and lymphocytes. The nuclear pattern of the giant cell formation process initially assumed a centrally located nuclear distribution of a foreign-body giant cell type, and then a peripherally located Langhans type distribution when the number of nuclei reached about five in both the mouse peritoneal space and the rabbit eye chambel'. Ultra-large giant cells containing a number of nuclei , however, were only obse.'ved on lenses implanted in the rabbit eye, demonstrating a difference between the two environments. Key Words: giant c 11 , intraocular lens, macrophage, nuclear pattern, phagocytosis
It is well known that macrophages display phagocytosis and play an essential role in the cellular response to implanted inert foreign bodies such as clinically used biomaterials.l-4 The cell usually assumes the form of an epithelioid cell accompanied by the formation of giant cells. 5-11 In previous papers in this series,12-15 we described a cellular response observed on the experimentally implanted intraocular lens (IOL). It was similar to the responses reported by Wolter and
other researchers. 16-29 Major cell components were macrophages and metamorphosed epithelioid cells with occasional formations of foreign-body giant cells from their fusion. Moderate numbers of lymphocytic clusters were seen on the IOL implanted in the mouse peritoneal space but were rarely detected on that implanted in the rabbit eye, indicating an environmental difference between these two sites. Macrophages and their related cells also exhibited weaker adhesiveness on the IOL in the rabbit eye.
From the Department of Ophthalmology, Wakayama Medical College,
~lakayama,
Japan.
Reprint requests to K. Uenoyama, M.D., Department of Ophthalmology, Wakayama Medical College, 7-Bancho 1, Wakayama, Japan 640. J CATARACT REFRACT SURG-VOL 16, JULY 1990
465
On an IOL implanted in the eye, macrophage behavior differs from its usual foreign-body response. Flattened sessile macrophages with membranous extensions of cytoplasm are observed forming an ultra-large giant cell approximately one half millimeter and containing a number of nuclei. In this paper we attempt to elucidate the phagocytic activities of macrophages observed on the implanted IOL during the process of giant cell formation, a process accompanied by a variety of nuclear patterns including ultra-large giant cells. MATERIALS AND METHODS
Rabbit and mouse implantation and fixation techniques have been previously described.l 2
For light microscopy, the removed IOL was fixed and stained without making sections by hematoxylin and eosin using Wolter's implant cytology technique. For scanning electron microscopy (SEM), the specimen was fixed in glutaraldehyde solution, dehydrated in a series of ethanol, and dried at critical point under liquid carbon dioxide. An Au-ion spattering was applied for final observation. For transmission electron microscopy, the removed IOL was treated in trypsin solution and the solution was centrifuged to obtain cellular sediment. The sediment was then fixed with osmic acid, dehydrated in a graded Durcupan (Ciba) series, and embedded in epoxyresin. After ultrathin sectioning, a dual staining with uranyl acetate and lead citrate was performed. RESULTS
Phagocytosis of Foreign Particles Macrophages, epithelioid cells, and giant cells demonstrated active phagocytosis on an IOL implanted in the mouse peritoneal space when foreign particles such as latex (see Figure 13 in Part II13) or carbon colloid (Figure 1) were injected at the time of implantation. As a phenomenon of the immune response in the mouse peritoneal space, central macrophages exhibited phagocytosis of carbon colloid while surrounding lymphocytes exhibited no such activity (Figure 1, A). Fibroblast-like cells also contained a number of carbon particles in their cytoplasm,
Fig. 1.
466
(U enoyama) Phagocytosis of carbon colloid by macrophages or related cells observed on a silicone plate implanted in the mouse peritoneal space and removed four days after surgery. Carbon colloid was injected at the time of implantation. A: A center macrophage (arrow) with surrounding lymphocytes (arrowheads) in the formation of a lymphocytic cluster in which only the macrophage exhibits phagocytosis of carbon colloid. B: A fibroblast-like cell (arrow) containing carbon particles (arrowheads) in its cytoplasm, indicating its macrophagic origin. C: A giant cell with phagocytized lymphocytes (arrow) and carbon particles (arrowheads) in its cytoplasm. Implant cytology staining (original magnification X 400).
Fig. 2.
(Uenoyama) Scanning electron micrograph of a stage in phagocytosis. A spindle-shaped fibroblast-like cell is being phagocytized by a macrophage characterized by a surface structure of marked microvilli. This was observed on a silicone plate implanted in the mouse peritoneal space and removed three days later (original magnification X 3,500).
J CATARACT REFRACT SURG- VOL 16, JULY 1990
Phagocytosis of Cells or of Cell Debris and Fusional Activities of Macrophages Cells such as erythrocytes, polymorphonuclear leukocytes, fibroblast-like cells, and lymphocytes were observed being engulfed by macrophages or related cells (Figures 1C and 2 in the mouse peritoneal space, Figures 3 and 4 in the rabbit eye). In the rabbit eye, although macrophages and related cells transformed themselves into a flattened shape in the aqueous humor, the cells exhibited various forms of phagocytosis and fusional activities (Figure 5, A through F).
Fig. 3.
(Uenoyama) Phagocytosis of polymorphonuclear leukocytes (arrow) by a giant cell observed on a poly (methyl methacrylate) IOL implanted in the rabbit eye and removed one week after surgery. Implant cytology staining (original magnification X 200).
indicating the macrophagic origin of these cells (Figure 1, B). Giant cells formed by the fusion of macrophages or epithelioid cells naturally contained phagocytized carbon particles in their cytoplasm (Figure 1, C).
Nuclear Patterns During Giant Cell Formation On the IOL implanted in the mouse peritoneal space, most giant cells exhibited a foreign-body giant cell nuclear pattern in which the nuclei of each cell were centrally located in the cytoplasm. At approximately five nuclei, however, the nuclei tended to be
A
B
c
Fig. 4
(Uenoyama) Transmission electron micrograph of a macrophage at the beginning of phagocytosis of an erythrocyte. The specimen was obtained through trypsin treatment from the surface of a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed one week later (original magnification X 8,800).
Fig. 5.
(U enoyama) Different stages of phagocytosis by macrophages and different stages of fusion by giant cells observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. A: A macrophage with a phagocytized small particle (possibly cellular debris, arrow) inside a cytoplasmic vacuole. B: An erythrocyte (arrow) phagocytized within the extended cytoplasm of a macrophage. C: A round macrophage in contact with an epithelioid cell with markedly extended cytoplasm indicating fusion of the two cells. D, E, F: Three different stages in the fusion of a macrophage by a giant cell. Implant cytology staining (original magnification X 1,000).
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Fig. 6.
(Uenoyama) Nuclear patterns in the process of giant cell formation (arrows) on a silicone plate implanted in the mouse peritoneal space and removed four days after. At stages characterized by three to five nuclei, the pattern showed a Langhans type nuclear distribution (C, D, and E). In the initial stages (A and B) and the later stage (F), nuclear patterns were of an ordinary foreign-body giant cell type. Implant cytology staining (original magnification X 400).
distributed peripherally, exhibiting a Langhans giant cell pattern (Figure 6, A through F). In the rabbit eye, two different nuclear pattern development processes were observed on the implanted IOL. One was similar to that observed on the IOL in the mouse peritoneal space-generally the foreign-body giant cell type except at nuclear numbers around five when the Langhans type predominated. In both cases, nuclei were always accompanied by well-demarcated and well-stained cytoplasm (Figure 7, A through F). The second process was that of ordinary foreign-body giant cells with centrally located nuclei regardless of the number. In these cases nuclei were accompanied by widely extended cytoplasmic membrane (Figure 8, A through I).
Formation of Ultra-Large Giant Cells Observed on the IOL Implanted in the Rabbit Eye On the IOL implanted in the rabbit eye for more than two weeks, ultra-large giant cells containing hundreds of nuclei were often observed. The cells 468
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Fig. 7.
(Uenoyama) Nuclear patterns in the process of giant cell formation observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. In these cells, characterized by wellstained and well-demarcated cytoplasm, the nuclear distribution was similar to those observed in the mouse peritoneal space, exhibiting Langhans type (D and E) in the intermediate stages of giant cell formation. Arrows indicate nuclei. Implant cytology staining (original magnification X 1,000).
were apparently formed by the fusion of ordinary sized giant cells (Figure 9, A) and contained a number of centrally located vacuoles, subsequently resulting in a pattern of many peripherally distributed nuclei (Figure 9, B through E) accompanied by an increasing extension of cytoplasm as a thin membrane covering a large area of the IOL surface (Figure 9, E and F). DISCUSSION Phagocytosis, a predominant activity of the mononuclear phagocytic system, is particularly important in the response to foreign bodies introduced into living tissues of the body.1,2,3 When an IOL is implanted in the eye, macrophages originating in the iris stroma (resident macrophages) play an active role in phagocytosis of foreign bodies or in immune response through antigen presentation. 15 The implanted IOL is a foreign body too large to be phagocytized by macrophages. When cell transformation occurs, the morphology includes epithe-
REFRACT SURG-VOL 16, JULY 1990
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• H
E
B
E
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•
.
&-.----------------~~--
Fig. 8.
.
(Uenoyama) Nuclear patterns in the process of giant cell formation observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. In these cells, characterized by thin staining and markedly extended cytoplasm, the nuclear distribution was similar to that in ordinary foreign-body giant-cell types. Implant cytology staining (original magnification x 400).
lioid cells, fibroblast-like cells, and even giant cells resulting from their fusion. The nuclear distribution of these giant cells also exhibited various patterns at the two implantation sites. Active DNA synthesis might be a determining factor from the results obtained in studying different agents affecting DNA transcription in the process of giant cell formation. 6 . 9 The formation of ultra-large giant cells was observed only on IOLs implanted in the rabbit eye chamber, not in the mouse peritoneal space, thus demonstrating an environmental difference between the two implantation sites. The marked extension of the cytoplasmic membrane observed in ultra-large giant cells, which covered large areas of the IOL surface, was characteristic of the rabbit eye chamber and was not observed on the IOL implanted in the mouse peritoneal space. This also suggests a difference in the foreign-body response of the two environments. REFERENCES 1. Marchesi VT. Inflammation and healing. In: Kissane JM, ed,
Anderson's Pathology, 8th ed, St Louis, CV Mosby Co, 1985; vol 1, 44-47 2. Bloom W, Fawcett DW. A Textbook of Histology, 11th ed. Philadelphia, WB Saunders, 1986; 16-17 3. Darnell J, Lodish H, Baltimore D. Molecular Cell Biology. New York, Scientific American Books Inc, 1986; 638-643
I
F
Fig. 9.
(Uenoyama) Nuclear pattern in the process of ultralarge giant cell formation observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. Several ordinary foreignbody giant cells were fused to each other (A). Formation of ultra-large giant cell with hundreds of nuclei. With marked vacuole formation, the nuclei were distributed rather peripherally (B-E) and the cell extended its cytoplasm as a thin membrane that covered a large area of the IOL surface (F). Implant cytology staining (original magnification X 200).
4. Sutton JS, Weiss L. Transformation of monocytes in tissue culture into macrophages, epithelioid cells, and multinucleated giant cells; an electron microscope study. J Cell Bioi 1966; 28:303-332 5. Papadimitriou JM, Spector WC. The origin, properties and fate of epithelioid cells. J Pathol 1971; 105:187-203 6. Papadimitriou JM, Sforsina D, Papaelias L. Kinetics of multinucleate giant cell formation and their modification by various agents in foreign body reactions. Am J Patho11973; 73:349-362 7. Papadimitriou JM, Finlay-Jones J-M, Walters MN-I. Surface characteristics of macrophages, epithelioid and giant cells using scanning electron microscopy. Exp Cell Res 1973; 76:353-362 8. Papadimitriou JM, Robertson TA, Walters MN-L An analysis of the phagocytic potential of multinucleate filreign body giant cells. Am J Pathol 1975; 78:343-358 9. Papadimitriou JM, Cornelisse CJ, A cytophotometric and autoradiographic study of DNA synthesis in macrophages and multinucleate foreign body giant cells. J Reticuloendothelial Soc 1975; 18:260-270 10. Papadimitriou JM, Wyche PA. A biochemical profile of glass-adherent cell populations containing multinucleated foreign body giant cells. J Pathol 1976; 119:239-254
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11. van der Rhee HJ, Hillebrands W, Daems WT. Are Langhans giant cells precursors of foreign-body giant cells? Arch Dermatol Res 1978; 263:13-21 12. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part I: Cellular components observed on the implanted lens surface. J Cataract Refract Surg 1988; 14:187-191 13. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part II: Morphological stages of the macrophage on the implanted lens surface. J Cataract Refract Surg 1988; 14:192-196 14. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part III: Giant cell formation on the implanted lens surface. J Cataract Refract Surg 1988; 14:197-201 15. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part IV: Cell adhesion, flbroblastlike cell, and lymphocytic cluster observed on the implanted lens surface. J Cataract Refract Surg 1989; 15:559-566 16. Wolter JR, Lichter PRo Fibroblast-like cells on intraocular lens implants: phagocytosing erythrocytes. Br J Ophthalmol 1983; 67:641-645 17. Wolter JR, Kunkel SL. Healon effect on the reactions of macrophages to a clear plastic surface. Ophthalmic Surg 1984; 15:298-301 18. Wolter JR. Cytopathology of intraocular lens implantation. Ophthalmology 1985; 92:135-142 19. \Volter JR. Foreign body giant cells on intraocular lens
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implants. Graefes Arch Clin Exp Ophthalmol 1982: 219:103-111 Wolter JR. Fusion of macrophages on lens implants resulting in the formation of giant cells. Graefes Arch Clin Exp Ophthalmol 1983; 221:1-7 McDonnell pJ, Green WR, Maumenee AE, Iliff WJ. Pathology of intraocular lenses in 33 eyes examined postmortem. Ophthalmology 1983; 90:386-403 Champion R, Green WR. Intraocular lenses: a histopathologic study of eyes, ocular tissues, and intraocular lenses obtained surgically. Ophthalmology 198,5; 92: 1628-1645 Sievers H, von Domarus D. Foreign-body reaction against intraocular lenses. Am J Ophthalmol1984; 97:743-751 Figueras MJ, Jongebloed WI, Worst JGF. Scanning electron microscopy study of experimental intraocular lens implantation in the rabbit eye. J Cataract Refract Surg 1986; 12:523-528 Menapace R, Juchem M, Skorpik C, Kulnig W. Clinicopathologic findings after in-the-bag implantation of open-loop polymethylmethacrylate and silicone lenses in the rabbit eye. J Cataract Refract Surg 1987; 13:630-634 Goder GJ, Volker-Dieben HJ. Microscopic-cytologic investigations on explanted intraocular lenses. Acta Ophthalmol 1985; suppl 170:64-72 Puck A, Tso MOM, Yue B. Cellular deposits on intraocular lenses. Acta Ophthalmol 1985; suppl 170:54-60 Kappelhof JP, Pameyer JH, De Jong PTVM, et al. The proteinaceous coating and cytology of implant lenses in rabbits. Am J Ophthalmol 1986; 102:750-758 Ishibashi T, Sugai S, Kubota T, et al. Cytopathology of early cellular reaction on implant lenses in monkeys. Graefes Arch Clin Exp Ophthalmol 1989; 227:470-475
SURG- VOL 16, JULY 1990
ABSTRACT The major cellular components on intraoculal' lenses experimentally implanted in the .'abbit eye and in the mouse peritoneal space were examined. They consisted of macrophages and their metamorphosed epithelioid cells with occasional formations of fOl'eignbody giant cells from the fusion of the macrophage-related cells. Lymphocytes, individually and in clusters , were also seen on the lenses implanted in the mouse peritoneal space but l'arely on those implanted in the rabbit eye. Macrophages, epithelioid cells, and giant cells exhibited active phagocytosis on the implanted intraocular lenses. These cells phagocytized not only minor foreign particles such as artificially fed latex 0., carbon colloids but also living cells including e.'ythrocytes, leukocytes, and lymphocytes. The nuclear pattern of the giant cell formation process initially assumed a centrally located nuclear distribution of a foreign-body giant cell type, and then a peripherally located Langhans type distribution when the number of nuclei reached about five in both the mouse peritoneal space and the rabbit eye chambel'. Ultra-large giant cells containing a number of nuclei , however, were only obse.'ved on lenses implanted in the rabbit eye, demonstrating a difference between the two environments. Key Words: giant c 11 , intraocular lens, macrophage, nuclear pattern, phagocytosis
It is well known that macrophages display phagocytosis and play an essential role in the cellular response to implanted inert foreign bodies such as clinically used biomaterials.l-4 The cell usually assumes the form of an epithelioid cell accompanied by the formation of giant cells. 5-11 In previous papers in this series,12-15 we described a cellular response observed on the experimentally implanted intraocular lens (IOL). It was similar to the responses reported by Wolter and
other researchers. 16-29 Major cell components were macrophages and metamorphosed epithelioid cells with occasional formations of foreign-body giant cells from their fusion. Moderate numbers of lymphocytic clusters were seen on the IOL implanted in the mouse peritoneal space but were rarely detected on that implanted in the rabbit eye, indicating an environmental difference between these two sites. Macrophages and their related cells also exhibited weaker adhesiveness on the IOL in the rabbit eye.
From the Department of Ophthalmology, Wakayama Medical College,
~lakayama,
Japan.
Reprint requests to K. Uenoyama, M.D., Department of Ophthalmology, Wakayama Medical College, 7-Bancho 1, Wakayama, Japan 640. J CATARACT REFRACT SURG-VOL 16, JULY 1990
465
On an IOL implanted in the eye, macrophage behavior differs from its usual foreign-body response. Flattened sessile macrophages with membranous extensions of cytoplasm are observed forming an ultra-large giant cell approximately one half millimeter and containing a number of nuclei. In this paper we attempt to elucidate the phagocytic activities of macrophages observed on the implanted IOL during the process of giant cell formation, a process accompanied by a variety of nuclear patterns including ultra-large giant cells. MATERIALS AND METHODS
Rabbit and mouse implantation and fixation techniques have been previously described.l 2
For light microscopy, the removed IOL was fixed and stained without making sections by hematoxylin and eosin using Wolter's implant cytology technique. For scanning electron microscopy (SEM), the specimen was fixed in glutaraldehyde solution, dehydrated in a series of ethanol, and dried at critical point under liquid carbon dioxide. An Au-ion spattering was applied for final observation. For transmission electron microscopy, the removed IOL was treated in trypsin solution and the solution was centrifuged to obtain cellular sediment. The sediment was then fixed with osmic acid, dehydrated in a graded Durcupan (Ciba) series, and embedded in epoxyresin. After ultrathin sectioning, a dual staining with uranyl acetate and lead citrate was performed. RESULTS
Phagocytosis of Foreign Particles Macrophages, epithelioid cells, and giant cells demonstrated active phagocytosis on an IOL implanted in the mouse peritoneal space when foreign particles such as latex (see Figure 13 in Part II13) or carbon colloid (Figure 1) were injected at the time of implantation. As a phenomenon of the immune response in the mouse peritoneal space, central macrophages exhibited phagocytosis of carbon colloid while surrounding lymphocytes exhibited no such activity (Figure 1, A). Fibroblast-like cells also contained a number of carbon particles in their cytoplasm,
Fig. 1.
466
(U enoyama) Phagocytosis of carbon colloid by macrophages or related cells observed on a silicone plate implanted in the mouse peritoneal space and removed four days after surgery. Carbon colloid was injected at the time of implantation. A: A center macrophage (arrow) with surrounding lymphocytes (arrowheads) in the formation of a lymphocytic cluster in which only the macrophage exhibits phagocytosis of carbon colloid. B: A fibroblast-like cell (arrow) containing carbon particles (arrowheads) in its cytoplasm, indicating its macrophagic origin. C: A giant cell with phagocytized lymphocytes (arrow) and carbon particles (arrowheads) in its cytoplasm. Implant cytology staining (original magnification X 400).
Fig. 2.
(Uenoyama) Scanning electron micrograph of a stage in phagocytosis. A spindle-shaped fibroblast-like cell is being phagocytized by a macrophage characterized by a surface structure of marked microvilli. This was observed on a silicone plate implanted in the mouse peritoneal space and removed three days later (original magnification X 3,500).
J CATARACT REFRACT SURG- VOL 16, JULY 1990
Phagocytosis of Cells or of Cell Debris and Fusional Activities of Macrophages Cells such as erythrocytes, polymorphonuclear leukocytes, fibroblast-like cells, and lymphocytes were observed being engulfed by macrophages or related cells (Figures 1C and 2 in the mouse peritoneal space, Figures 3 and 4 in the rabbit eye). In the rabbit eye, although macrophages and related cells transformed themselves into a flattened shape in the aqueous humor, the cells exhibited various forms of phagocytosis and fusional activities (Figure 5, A through F).
Fig. 3.
(Uenoyama) Phagocytosis of polymorphonuclear leukocytes (arrow) by a giant cell observed on a poly (methyl methacrylate) IOL implanted in the rabbit eye and removed one week after surgery. Implant cytology staining (original magnification X 200).
indicating the macrophagic origin of these cells (Figure 1, B). Giant cells formed by the fusion of macrophages or epithelioid cells naturally contained phagocytized carbon particles in their cytoplasm (Figure 1, C).
Nuclear Patterns During Giant Cell Formation On the IOL implanted in the mouse peritoneal space, most giant cells exhibited a foreign-body giant cell nuclear pattern in which the nuclei of each cell were centrally located in the cytoplasm. At approximately five nuclei, however, the nuclei tended to be
A
B
c
Fig. 4
(Uenoyama) Transmission electron micrograph of a macrophage at the beginning of phagocytosis of an erythrocyte. The specimen was obtained through trypsin treatment from the surface of a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed one week later (original magnification X 8,800).
Fig. 5.
(U enoyama) Different stages of phagocytosis by macrophages and different stages of fusion by giant cells observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. A: A macrophage with a phagocytized small particle (possibly cellular debris, arrow) inside a cytoplasmic vacuole. B: An erythrocyte (arrow) phagocytized within the extended cytoplasm of a macrophage. C: A round macrophage in contact with an epithelioid cell with markedly extended cytoplasm indicating fusion of the two cells. D, E, F: Three different stages in the fusion of a macrophage by a giant cell. Implant cytology staining (original magnification X 1,000).
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Fig. 6.
(Uenoyama) Nuclear patterns in the process of giant cell formation (arrows) on a silicone plate implanted in the mouse peritoneal space and removed four days after. At stages characterized by three to five nuclei, the pattern showed a Langhans type nuclear distribution (C, D, and E). In the initial stages (A and B) and the later stage (F), nuclear patterns were of an ordinary foreign-body giant cell type. Implant cytology staining (original magnification X 400).
distributed peripherally, exhibiting a Langhans giant cell pattern (Figure 6, A through F). In the rabbit eye, two different nuclear pattern development processes were observed on the implanted IOL. One was similar to that observed on the IOL in the mouse peritoneal space-generally the foreign-body giant cell type except at nuclear numbers around five when the Langhans type predominated. In both cases, nuclei were always accompanied by well-demarcated and well-stained cytoplasm (Figure 7, A through F). The second process was that of ordinary foreign-body giant cells with centrally located nuclei regardless of the number. In these cases nuclei were accompanied by widely extended cytoplasmic membrane (Figure 8, A through I).
Formation of Ultra-Large Giant Cells Observed on the IOL Implanted in the Rabbit Eye On the IOL implanted in the rabbit eye for more than two weeks, ultra-large giant cells containing hundreds of nuclei were often observed. The cells 468
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A
o
B
E
c
F
Fig. 7.
(Uenoyama) Nuclear patterns in the process of giant cell formation observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. In these cells, characterized by wellstained and well-demarcated cytoplasm, the nuclear distribution was similar to those observed in the mouse peritoneal space, exhibiting Langhans type (D and E) in the intermediate stages of giant cell formation. Arrows indicate nuclei. Implant cytology staining (original magnification X 1,000).
were apparently formed by the fusion of ordinary sized giant cells (Figure 9, A) and contained a number of centrally located vacuoles, subsequently resulting in a pattern of many peripherally distributed nuclei (Figure 9, B through E) accompanied by an increasing extension of cytoplasm as a thin membrane covering a large area of the IOL surface (Figure 9, E and F). DISCUSSION Phagocytosis, a predominant activity of the mononuclear phagocytic system, is particularly important in the response to foreign bodies introduced into living tissues of the body.1,2,3 When an IOL is implanted in the eye, macrophages originating in the iris stroma (resident macrophages) play an active role in phagocytosis of foreign bodies or in immune response through antigen presentation. 15 The implanted IOL is a foreign body too large to be phagocytized by macrophages. When cell transformation occurs, the morphology includes epithe-
REFRACT SURG-VOL 16, JULY 1990
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• H
E
B
E
c
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•
.
&-.----------------~~--
Fig. 8.
.
(Uenoyama) Nuclear patterns in the process of giant cell formation observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. In these cells, characterized by thin staining and markedly extended cytoplasm, the nuclear distribution was similar to that in ordinary foreign-body giant-cell types. Implant cytology staining (original magnification x 400).
lioid cells, fibroblast-like cells, and even giant cells resulting from their fusion. The nuclear distribution of these giant cells also exhibited various patterns at the two implantation sites. Active DNA synthesis might be a determining factor from the results obtained in studying different agents affecting DNA transcription in the process of giant cell formation. 6 . 9 The formation of ultra-large giant cells was observed only on IOLs implanted in the rabbit eye chamber, not in the mouse peritoneal space, thus demonstrating an environmental difference between the two implantation sites. The marked extension of the cytoplasmic membrane observed in ultra-large giant cells, which covered large areas of the IOL surface, was characteristic of the rabbit eye chamber and was not observed on the IOL implanted in the mouse peritoneal space. This also suggests a difference in the foreign-body response of the two environments. REFERENCES 1. Marchesi VT. Inflammation and healing. In: Kissane JM, ed,
Anderson's Pathology, 8th ed, St Louis, CV Mosby Co, 1985; vol 1, 44-47 2. Bloom W, Fawcett DW. A Textbook of Histology, 11th ed. Philadelphia, WB Saunders, 1986; 16-17 3. Darnell J, Lodish H, Baltimore D. Molecular Cell Biology. New York, Scientific American Books Inc, 1986; 638-643
I
F
Fig. 9.
(Uenoyama) Nuclear pattern in the process of ultralarge giant cell formation observed on a poly(methyl methacrylate) IOL implanted in the rabbit eye and removed two weeks later. Several ordinary foreignbody giant cells were fused to each other (A). Formation of ultra-large giant cell with hundreds of nuclei. With marked vacuole formation, the nuclei were distributed rather peripherally (B-E) and the cell extended its cytoplasm as a thin membrane that covered a large area of the IOL surface (F). Implant cytology staining (original magnification X 200).
4. Sutton JS, Weiss L. Transformation of monocytes in tissue culture into macrophages, epithelioid cells, and multinucleated giant cells; an electron microscope study. J Cell Bioi 1966; 28:303-332 5. Papadimitriou JM, Spector WC. The origin, properties and fate of epithelioid cells. J Pathol 1971; 105:187-203 6. Papadimitriou JM, Sforsina D, Papaelias L. Kinetics of multinucleate giant cell formation and their modification by various agents in foreign body reactions. Am J Patho11973; 73:349-362 7. Papadimitriou JM, Finlay-Jones J-M, Walters MN-I. Surface characteristics of macrophages, epithelioid and giant cells using scanning electron microscopy. Exp Cell Res 1973; 76:353-362 8. Papadimitriou JM, Robertson TA, Walters MN-L An analysis of the phagocytic potential of multinucleate filreign body giant cells. Am J Pathol 1975; 78:343-358 9. Papadimitriou JM, Cornelisse CJ, A cytophotometric and autoradiographic study of DNA synthesis in macrophages and multinucleate foreign body giant cells. J Reticuloendothelial Soc 1975; 18:260-270 10. Papadimitriou JM, Wyche PA. A biochemical profile of glass-adherent cell populations containing multinucleated foreign body giant cells. J Pathol 1976; 119:239-254
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11. van der Rhee HJ, Hillebrands W, Daems WT. Are Langhans giant cells precursors of foreign-body giant cells? Arch Dermatol Res 1978; 263:13-21 12. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part I: Cellular components observed on the implanted lens surface. J Cataract Refract Surg 1988; 14:187-191 13. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part II: Morphological stages of the macrophage on the implanted lens surface. J Cataract Refract Surg 1988; 14:192-196 14. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part III: Giant cell formation on the implanted lens surface. J Cataract Refract Surg 1988; 14:197-201 15. Uenoyama K, Kanagawa R, Tamura M, et al. Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part IV: Cell adhesion, flbroblastlike cell, and lymphocytic cluster observed on the implanted lens surface. J Cataract Refract Surg 1989; 15:559-566 16. Wolter JR, Lichter PRo Fibroblast-like cells on intraocular lens implants: phagocytosing erythrocytes. Br J Ophthalmol 1983; 67:641-645 17. Wolter JR, Kunkel SL. Healon effect on the reactions of macrophages to a clear plastic surface. Ophthalmic Surg 1984; 15:298-301 18. Wolter JR. Cytopathology of intraocular lens implantation. Ophthalmology 1985; 92:135-142 19. \Volter JR. Foreign body giant cells on intraocular lens
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23. 24.
25.
26. 27. 28. 29.
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