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Significance of Growth Rates in the Development of the Eye*
SIGNIFICANCE OF GROWTH RATES IN T H E DEVELOPMENT OF T H E EYE* AELETA N. ; MtBER, P H . D .
New Orlea r, Louisiana
Our attention was drawn to the signifi cance of alterations in the growth potentials in embryonic development by a study of the histogenesis of congenital anophthalmia in a strain of mice used in our experimental inves tigations. The inbred adult mice show 100percent total anophthalmia but hybrids of the first generation have normal eyes. When mothers of the hybrids are treated with teratogens on certain days in gestation, a percentage of their young have defective eyes. Careful examination of these embryos at various stages in development reveal that the eye develops normally to a certain stage ; after which, if the initial injury has not re sulted in death and absorption of the optic vesicle and lens, it becomes completely sepa rated from the surface of the head by pre mature and accelerated ingrowth of the paraxial mesoderm and may even become en closed within the skull. The analogy between the fundamental processes involved in the production of anophthalmia in these mice and a previous dissection of a case of hu man cyclopia seems apparent and offers an explanation of the possible course of events in certain cases of human teratology. MATERIALS AND METHODS
The anophthalmic strain of mice (Zrd) maintained in this laboratory were originally obtained from the Roscoe B. Jackson Lab oratory in 1950 in the F17 generation and have been kept inbred by brother-sister matings. Two colonies of mice having normal eyes are also maintained; DBA/2 received * From the Department of Pathology, Louisiana State University School of Medicine. This in vestigation was supported by research grants B-136 and B-876 from the National Institute of Neuro logical Diseases and Blindness of the National In stitutes of Health, United States Public Health Service.
at the same time from the same source in the F 4 0 generation, and C57 black mice in the F 3 1 generation. The standard for gesta tion age is by timed matings confirmed by vaginal plugs. Serial sections of the eye region of normal and anophthalmic em bryos were made throughout gestation for the study of the histogenesis of the defect and comparison with sections of defective eyes in hybrid embryos whose mothers had been treated with trypan blue, cortisone, or injections of brain emulsions. The details of these treatments were published in a pre vious report.3 DESCRIPTION OF EYE DEVELOPMENT
In the mouse, the lens plate normally de velops on the 10th day of gestation and invaginates to form a vesicle by the 11th day. It separates from the surface epithelium late on the same day and sinks inward to fill the cavity of the optic cup. Mesoderm grows forward, filling the space between the lens vesicle and epithelium, and condenses to form the stroma of the cornea during the 13th day. The anterior chamber is present by the 14th day (figs. 1, 3 and 5). The first evidence of deviation from normal development in the eyes of the blind mice is visible in sections of the lens plate on the 11th day in gestation. The cells in the center of the plate lose their polarity, become irregularly packed together and in vagination is delayed. Invagination occurs on the 12th day but the cells remain ir regularly arranged and the vesicle is elon gated (figs. 2, 4 and 6 ) . The lens vesicle continues to elongate and does not separate from the epithelium until late on the 14th day. The mesodermal cells surrounding the optic vesicle remain closely packed and stel late in shape. No cornea or anterior cham ber is formed (fig. 7).
GROWTH RATES AND THE EYE
Fig. 1 (Barber). Sagittal section through the lens plate and optic vesicle of a control mouse embryo on the 10th day in gestation. The lens plate is invaginating to form a smoothly rounded vesicle. In some cases the optic cup remains small, the number of mitotic divisions is reduced and the eye may undergo varying degrees of absorption or it may remain fairly normal
Fig. 2 (Barber). Sagittal section through the lens plate and optic vesicle of a Zrd (blind) mouse embryo on the 11th day in gestation. The cells of the lens plate are tightly drawn together, forming an elongated pocket.
763
I'iu 3 (Barber). Sagittal section through the eye of an 11-day control mouse embryo. The lens vesicle has separated from the surface ectoderm and fills the cavity of the optic cup. in size and become surrounded by the in growing mesoderm ("buried eye"). The condition is always bilateral in the Zrd strain; and, even in instances of complete
l'i. 1 ( ü u K r ) Hor.^Mi'ijl --tjiijii tinijii^h the eye of a 13-day embryo from the anophthalmic strain. The lens vesicle is still attached to the sur face epithelium and the optic cup is smaller than usual for this age. Mitoses are rare and amor phous granules are present in the retinal tissue.
764
AELETA
.BARBER
Fig. 5 (Barber). Horizontal section through the eye of a 14-day control embryo. The cornea is formed and the anterior chamber is present. Precartilaginous formation of the optic foramen can be seen at (C).
absorption, the extrinsic eye muscles can be recognized. The final position of the eyes in the blind strain varies. They may be located in the orbit, or they may be more deeply buried, filling and distorting the optic fora men. They are never functional (figs. 7 and 8). Figures 9, 10 and 11 show examples of the position of defective eyes in hybrid em bryos whose mothers were treated with a teratogenic agent during gestation. When the condition is induced by a teratogen, the defect may be unilateral or bilateral. In some
Fig. 6 (Barber). Sagittal section through the lens of a 14-day embryo from the anophthalmic strain. The deformed lens is still attached to the surface by a slender thread and the mesodermal cells surrounding it are closely packed and stellate in shape.
Fig. 7 (Barber). Horizontal section through the head of a 17-day embryo from the anophthalmic strain. The eyes are fairly normal in size, both lenses are present, and the eyes are deeply buried. The extrinsic muscles are present.
cases the eye is located inside the skull and may even project into the cavity of the third ventricle. An eye is this position has not been discovered except in hybrids following maternal treatment with teratogens.
head of an 18-day embryo from the anophthalmic strain. Almost complete absorption of both eyes has occurred, leaving only a few remnants of ret inal tissue and pigment. The orbits are filled with mesodermal tissue and extrinsic muscles. (P) Pig ment.
GROWTH RATES AND T H E EYE
765
DISCUSSION
One of the basic tenets of embryology is that every individual germ, according to its genetic constitution, possesses an innate growth potential which remains the funda mental standard for all further develop ment.1 The growth rates of the mammalian embryo are nicely synchronized, and any alteration in their ratio results in defective development. A previous dissection of a case of human cyclopia demonstrated that altera tion in growth rates of the primordial tis sues resulted in spatial separation of the tissues contributing to the formation of the eye.2 Our recent observations on induced blindness in hybrid mice carrying recessive factors for anophthalmia indicate that a change in the rate of growth of the mesoderm may explain the development of a "buried" eye in these mice, and also serve to illustrate the consequences of such a change in the formation of the human eye. The course of events in the production of the eye defect in the inbred strain of Zrd mice seems to be due to an initial injury just prior to the formation of the lens plate and involves the entire eye-field. It is in herent in the genetic constitution of these mice and may be mediated through control
Fig. 9 (Barber). Horizontal section through the head of an 18-day hybrid embryo whose mother received injections of cortisone. Development of the lens and retina are within fairly normal lim its and aberrant nerve fibers from the retina are seen entering the chiasma.
Fig. 10 (Barber). Horizontal section through the head of an 18-day hybrid embryo whose mother received injections of trypan blue during gestation. One eye distorts the optic foramen and encroaches on the cavity of the third ventricle.
of enzymes, hormones, antigens, or possibly other metabolic processes. At any rate, the subsequent condition of the eye appears to be conditioned by the severity of the injury. If the insult to the eye-forming tissues is extreme, the cells of the lens plate and the optic vesicle are killed and are gradually absorbed. The paraxial mesoderm, which grows in later is not damaged, but is stim ulated and fills in the defect. On the other
Fig. 11 (Barber). Horizontal section through the head of an 18-day hybrid embryo whose mother was sensitized by injections of brain emulsions. The retina and lens are developed but the eye de forms the bones of the skull and projects into the cavity of the third ventricle.
766
AELETA N. BARBER
hand, when the initial injury is less severe, the lens and optic vesicle remain undam aged; and the ingrowth of mesoderm is ac celerated and is excessive in amount. Thus the undamaged eye becomes separated from the surface of the head and is deeply buried. When the Zrd mice are crossed with mice having factors for normal eyes, the hybrids of the first generation always have normally developed eyes. However, when their mothers are treated with a teratogenic agent during gestation, a certain percentage of the young develop defective eyes. In this in stance, the initial injury to the eye-field seems to be exaggerated ; and, if the cells of the lens plate and optic vesicle are not killed, ingrowth of the paraxial mesoderm becomes unduly stimulated and the eye be comes incarcerated either in the optic fora men or enclosed within the skull. The fact that the lens is present signifies that the optic vesicle came in contact with the sur face ectoderm at the proper time in order for a lens plate to be induced. The healthy condition of the cells of the retina, optic stalk and lens indicates that the noxious effect of the injury was not strong enough to destroy these structures. It seems ap parent that the initial injury must upset the normal synchronization of the growth rates of the eye-forming tissues so that the growth of the paraxial mesoderm far out strips the growth of the optic vesicle and lens. The evidence against retardation in the development of the lens and optic vesicle as being the major factor in the formation of this defect consists in the almost normal size of the eye and the healthy condition of the cells even when developed in an abnormal site (figs. 9, 10 and 11). Correlation of teratogenesis in humans and animals must be made with care; how ever, the fundamental processes of develop ment in mammalian embryos are very similar and consistent. Synchronization in growth rates in organogenesis is very exact, and any interference with these processes results in the formation of misplaced tissues
and organs. In the previous case of human cyclopia studied in this laboratory and pub lished in 1950,2 the neural portion of the eye was discovered to be buried in the bones forming the floor of the orbit; while the structures derived from mesoderm were located in the fused orbits. Also the ectodermal portion of the hypophysis had de veloped at a site widely separated from the neural portion. The injury was thought to have been received very early in pregnancy and to have produced a change in the normal growth rates which resulted in separation of the individual tissues of these organs. The analogy between these conditions, that is, enclosure of the eye by the bones of the optic foramen and skull in the mice, and separation of the individual elements of the eye and hypophysis in the human fetus, seems to be explained by acceleration in the growth of one tissue at the expense of another. Ac cording to Mann, 4 anophthalmia is rare in humans and can be caused either by suppres sion of the primary optic centers or second arily by injury to the optic vesicle followed by degeneration. The defect in our mice is not due to either of these conditions but clearly results from spatial separation of the tissues that form the eye. The findings in these mice suggests another manner in which anophthalmia may be brought about in a mammalian embryo. An interesting approach to this problem has been suggested by Walker,5 and Walker and Fraser 6 in their studies on the signifi cance of mucopolysaccharides in the mor phogenesis of palate development in mice. Runner 7 also described the action of teratogens on the morphogenesis of precartilaginous mesenchyme. The appearance of car tilage in the formation of the optic foramen in a 14-day embryo from the normal strain is seen in Figure 5 ; and in Figure 7, the carti lage of a deformed foramen is visible. Studies designed to follow the early de velopment of mesenchymal tissues of the orbit and optic foramen are now in progress
GROWTH RATES AND THE EYE and may yield information on the growth rates of the various tissues. SUMMARY
1. The histology of anophthalmia in a strain of mice has been described and com pared with normal development of the eye in the same species. 2. In some instances, the mesoderm in the eye region of hybrid mice whose mothers are given a teratogenic agent during gesta tion is accelerated at the expense of the neural portion of the eye, which then be comes separated from the surface of the
767
head and incarcerated in bone formation. 3. A pattern of similarity was noted be tween the fundamental embryonic processes involved in the production of blindness in these mice and a previously reported case of human cyclopia in which a change in the growth potential of the eye-forming tissues was postulated as the initial deviation from normal development. It is suggested that al teration in the growth rates of the tissues contributing to the formation of the eye may be responsible for certain cases of anophthalmia in humans. 1542 Tulane Avenue (12).
REFERENCES
1. Weiss, P.: Principles of Development. New York, Henry Holt, 1939. 2. Barber, A. N., and Muelling, R. J., Jr.: Cyclopia with complete separation of the neural and mesodermal elements of the eye. Arch. Ophth., 43:989, 1950. 3. Barber, A. N., Afeman, C, and Willis, J. : Inheritance of congenital anophthalmia in mice. Am. J. Ophth., 48:763, 1959. 4. Mann, I.: Developmental Abnormalities of the Eye. London, W. C. 1, British Medical Association, B.M.A. House, Tavistock Square, 1957, ed. 2. 5. Walker, B. E.: The association of mucopolysaccharides with morphogenesis of the palate and other structures in mouse embryos. J. Embryol. & Exper. Morphol., 9:22, 1961. 6. Walker, B. E., and Fraser, F. C. : Closure of the secondary palate in three strains of mice. J. Embryol. & Exper. Morphol., 4:176, 1956. 7. Runner, M. N.: Inheritance of susceptibility to congenital deformity. Metabolic clues provided by experiments with teratogenic agents. Pediatrics, 23:254, 1959.
EYE COMPLAINTS AS SYMPTOMS O F PSYCHIATRIC DISORDER* J O H N CLANCY,
M.D.
Iowa City, Iowa
The diagnostic and statistical manual, Mental Disorders,1 prepared by the Ameri can Psychiatric Association, contains no special section on psychiatric conditions affecting the eye. It is recognized that emo tional factors may play a causative role in disturbances of many organs and organ systems, and localized complaints are re garded as symptoms of the total reaction of the personality. Functional disturbances are first classified according to type of reaction and secondly as to symptom location. In every-day speech, however, the eye is credited with properties ♦From the Department of Psychiatry, College of Medicine, State University of Iowa.
and behavior which have little to do with its primary function and, for the sake of com pleteness, I have endeavored to classify these "aberrant functions." Three divisions suggested themselves: (1) emotional eyes, (2) behavioristic eyes, (3) miscellaneous eyes. In the first group I included the evil eyes, baleful eyes, green and envious eyes, red and tearful eyes, jaundiced eyes, and so forth. In the second group came the bulging eyes, popping eyes, searching eyes, penetrating eyes, roving eyes, loving eyes and lecherous eyes. The miscellaneous column listed the hungry eyes, the private eyes and bedroom eyes, to name a few. Such an exercise in nonsense at once
New Orlea r, Louisiana
Our attention was drawn to the signifi cance of alterations in the growth potentials in embryonic development by a study of the histogenesis of congenital anophthalmia in a strain of mice used in our experimental inves tigations. The inbred adult mice show 100percent total anophthalmia but hybrids of the first generation have normal eyes. When mothers of the hybrids are treated with teratogens on certain days in gestation, a percentage of their young have defective eyes. Careful examination of these embryos at various stages in development reveal that the eye develops normally to a certain stage ; after which, if the initial injury has not re sulted in death and absorption of the optic vesicle and lens, it becomes completely sepa rated from the surface of the head by pre mature and accelerated ingrowth of the paraxial mesoderm and may even become en closed within the skull. The analogy between the fundamental processes involved in the production of anophthalmia in these mice and a previous dissection of a case of hu man cyclopia seems apparent and offers an explanation of the possible course of events in certain cases of human teratology. MATERIALS AND METHODS
The anophthalmic strain of mice (Zrd) maintained in this laboratory were originally obtained from the Roscoe B. Jackson Lab oratory in 1950 in the F17 generation and have been kept inbred by brother-sister matings. Two colonies of mice having normal eyes are also maintained; DBA/2 received * From the Department of Pathology, Louisiana State University School of Medicine. This in vestigation was supported by research grants B-136 and B-876 from the National Institute of Neuro logical Diseases and Blindness of the National In stitutes of Health, United States Public Health Service.
at the same time from the same source in the F 4 0 generation, and C57 black mice in the F 3 1 generation. The standard for gesta tion age is by timed matings confirmed by vaginal plugs. Serial sections of the eye region of normal and anophthalmic em bryos were made throughout gestation for the study of the histogenesis of the defect and comparison with sections of defective eyes in hybrid embryos whose mothers had been treated with trypan blue, cortisone, or injections of brain emulsions. The details of these treatments were published in a pre vious report.3 DESCRIPTION OF EYE DEVELOPMENT
In the mouse, the lens plate normally de velops on the 10th day of gestation and invaginates to form a vesicle by the 11th day. It separates from the surface epithelium late on the same day and sinks inward to fill the cavity of the optic cup. Mesoderm grows forward, filling the space between the lens vesicle and epithelium, and condenses to form the stroma of the cornea during the 13th day. The anterior chamber is present by the 14th day (figs. 1, 3 and 5). The first evidence of deviation from normal development in the eyes of the blind mice is visible in sections of the lens plate on the 11th day in gestation. The cells in the center of the plate lose their polarity, become irregularly packed together and in vagination is delayed. Invagination occurs on the 12th day but the cells remain ir regularly arranged and the vesicle is elon gated (figs. 2, 4 and 6 ) . The lens vesicle continues to elongate and does not separate from the epithelium until late on the 14th day. The mesodermal cells surrounding the optic vesicle remain closely packed and stel late in shape. No cornea or anterior cham ber is formed (fig. 7).
GROWTH RATES AND THE EYE
Fig. 1 (Barber). Sagittal section through the lens plate and optic vesicle of a control mouse embryo on the 10th day in gestation. The lens plate is invaginating to form a smoothly rounded vesicle. In some cases the optic cup remains small, the number of mitotic divisions is reduced and the eye may undergo varying degrees of absorption or it may remain fairly normal
Fig. 2 (Barber). Sagittal section through the lens plate and optic vesicle of a Zrd (blind) mouse embryo on the 11th day in gestation. The cells of the lens plate are tightly drawn together, forming an elongated pocket.
763
I'iu 3 (Barber). Sagittal section through the eye of an 11-day control mouse embryo. The lens vesicle has separated from the surface ectoderm and fills the cavity of the optic cup. in size and become surrounded by the in growing mesoderm ("buried eye"). The condition is always bilateral in the Zrd strain; and, even in instances of complete
l'i. 1 ( ü u K r ) Hor.^Mi'ijl --tjiijii tinijii^h the eye of a 13-day embryo from the anophthalmic strain. The lens vesicle is still attached to the sur face epithelium and the optic cup is smaller than usual for this age. Mitoses are rare and amor phous granules are present in the retinal tissue.
764
AELETA
.BARBER
Fig. 5 (Barber). Horizontal section through the eye of a 14-day control embryo. The cornea is formed and the anterior chamber is present. Precartilaginous formation of the optic foramen can be seen at (C).
absorption, the extrinsic eye muscles can be recognized. The final position of the eyes in the blind strain varies. They may be located in the orbit, or they may be more deeply buried, filling and distorting the optic fora men. They are never functional (figs. 7 and 8). Figures 9, 10 and 11 show examples of the position of defective eyes in hybrid em bryos whose mothers were treated with a teratogenic agent during gestation. When the condition is induced by a teratogen, the defect may be unilateral or bilateral. In some
Fig. 6 (Barber). Sagittal section through the lens of a 14-day embryo from the anophthalmic strain. The deformed lens is still attached to the surface by a slender thread and the mesodermal cells surrounding it are closely packed and stellate in shape.
Fig. 7 (Barber). Horizontal section through the head of a 17-day embryo from the anophthalmic strain. The eyes are fairly normal in size, both lenses are present, and the eyes are deeply buried. The extrinsic muscles are present.
cases the eye is located inside the skull and may even project into the cavity of the third ventricle. An eye is this position has not been discovered except in hybrids following maternal treatment with teratogens.
head of an 18-day embryo from the anophthalmic strain. Almost complete absorption of both eyes has occurred, leaving only a few remnants of ret inal tissue and pigment. The orbits are filled with mesodermal tissue and extrinsic muscles. (P) Pig ment.
GROWTH RATES AND T H E EYE
765
DISCUSSION
One of the basic tenets of embryology is that every individual germ, according to its genetic constitution, possesses an innate growth potential which remains the funda mental standard for all further develop ment.1 The growth rates of the mammalian embryo are nicely synchronized, and any alteration in their ratio results in defective development. A previous dissection of a case of human cyclopia demonstrated that altera tion in growth rates of the primordial tis sues resulted in spatial separation of the tissues contributing to the formation of the eye.2 Our recent observations on induced blindness in hybrid mice carrying recessive factors for anophthalmia indicate that a change in the rate of growth of the mesoderm may explain the development of a "buried" eye in these mice, and also serve to illustrate the consequences of such a change in the formation of the human eye. The course of events in the production of the eye defect in the inbred strain of Zrd mice seems to be due to an initial injury just prior to the formation of the lens plate and involves the entire eye-field. It is in herent in the genetic constitution of these mice and may be mediated through control
Fig. 9 (Barber). Horizontal section through the head of an 18-day hybrid embryo whose mother received injections of cortisone. Development of the lens and retina are within fairly normal lim its and aberrant nerve fibers from the retina are seen entering the chiasma.
Fig. 10 (Barber). Horizontal section through the head of an 18-day hybrid embryo whose mother received injections of trypan blue during gestation. One eye distorts the optic foramen and encroaches on the cavity of the third ventricle.
of enzymes, hormones, antigens, or possibly other metabolic processes. At any rate, the subsequent condition of the eye appears to be conditioned by the severity of the injury. If the insult to the eye-forming tissues is extreme, the cells of the lens plate and the optic vesicle are killed and are gradually absorbed. The paraxial mesoderm, which grows in later is not damaged, but is stim ulated and fills in the defect. On the other
Fig. 11 (Barber). Horizontal section through the head of an 18-day hybrid embryo whose mother was sensitized by injections of brain emulsions. The retina and lens are developed but the eye de forms the bones of the skull and projects into the cavity of the third ventricle.
766
AELETA N. BARBER
hand, when the initial injury is less severe, the lens and optic vesicle remain undam aged; and the ingrowth of mesoderm is ac celerated and is excessive in amount. Thus the undamaged eye becomes separated from the surface of the head and is deeply buried. When the Zrd mice are crossed with mice having factors for normal eyes, the hybrids of the first generation always have normally developed eyes. However, when their mothers are treated with a teratogenic agent during gestation, a certain percentage of the young develop defective eyes. In this in stance, the initial injury to the eye-field seems to be exaggerated ; and, if the cells of the lens plate and optic vesicle are not killed, ingrowth of the paraxial mesoderm becomes unduly stimulated and the eye be comes incarcerated either in the optic fora men or enclosed within the skull. The fact that the lens is present signifies that the optic vesicle came in contact with the sur face ectoderm at the proper time in order for a lens plate to be induced. The healthy condition of the cells of the retina, optic stalk and lens indicates that the noxious effect of the injury was not strong enough to destroy these structures. It seems ap parent that the initial injury must upset the normal synchronization of the growth rates of the eye-forming tissues so that the growth of the paraxial mesoderm far out strips the growth of the optic vesicle and lens. The evidence against retardation in the development of the lens and optic vesicle as being the major factor in the formation of this defect consists in the almost normal size of the eye and the healthy condition of the cells even when developed in an abnormal site (figs. 9, 10 and 11). Correlation of teratogenesis in humans and animals must be made with care; how ever, the fundamental processes of develop ment in mammalian embryos are very similar and consistent. Synchronization in growth rates in organogenesis is very exact, and any interference with these processes results in the formation of misplaced tissues
and organs. In the previous case of human cyclopia studied in this laboratory and pub lished in 1950,2 the neural portion of the eye was discovered to be buried in the bones forming the floor of the orbit; while the structures derived from mesoderm were located in the fused orbits. Also the ectodermal portion of the hypophysis had de veloped at a site widely separated from the neural portion. The injury was thought to have been received very early in pregnancy and to have produced a change in the normal growth rates which resulted in separation of the individual tissues of these organs. The analogy between these conditions, that is, enclosure of the eye by the bones of the optic foramen and skull in the mice, and separation of the individual elements of the eye and hypophysis in the human fetus, seems to be explained by acceleration in the growth of one tissue at the expense of another. Ac cording to Mann, 4 anophthalmia is rare in humans and can be caused either by suppres sion of the primary optic centers or second arily by injury to the optic vesicle followed by degeneration. The defect in our mice is not due to either of these conditions but clearly results from spatial separation of the tissues that form the eye. The findings in these mice suggests another manner in which anophthalmia may be brought about in a mammalian embryo. An interesting approach to this problem has been suggested by Walker,5 and Walker and Fraser 6 in their studies on the signifi cance of mucopolysaccharides in the mor phogenesis of palate development in mice. Runner 7 also described the action of teratogens on the morphogenesis of precartilaginous mesenchyme. The appearance of car tilage in the formation of the optic foramen in a 14-day embryo from the normal strain is seen in Figure 5 ; and in Figure 7, the carti lage of a deformed foramen is visible. Studies designed to follow the early de velopment of mesenchymal tissues of the orbit and optic foramen are now in progress
GROWTH RATES AND THE EYE and may yield information on the growth rates of the various tissues. SUMMARY
1. The histology of anophthalmia in a strain of mice has been described and com pared with normal development of the eye in the same species. 2. In some instances, the mesoderm in the eye region of hybrid mice whose mothers are given a teratogenic agent during gesta tion is accelerated at the expense of the neural portion of the eye, which then be comes separated from the surface of the
767
head and incarcerated in bone formation. 3. A pattern of similarity was noted be tween the fundamental embryonic processes involved in the production of blindness in these mice and a previously reported case of human cyclopia in which a change in the growth potential of the eye-forming tissues was postulated as the initial deviation from normal development. It is suggested that al teration in the growth rates of the tissues contributing to the formation of the eye may be responsible for certain cases of anophthalmia in humans. 1542 Tulane Avenue (12).
REFERENCES
1. Weiss, P.: Principles of Development. New York, Henry Holt, 1939. 2. Barber, A. N., and Muelling, R. J., Jr.: Cyclopia with complete separation of the neural and mesodermal elements of the eye. Arch. Ophth., 43:989, 1950. 3. Barber, A. N., Afeman, C, and Willis, J. : Inheritance of congenital anophthalmia in mice. Am. J. Ophth., 48:763, 1959. 4. Mann, I.: Developmental Abnormalities of the Eye. London, W. C. 1, British Medical Association, B.M.A. House, Tavistock Square, 1957, ed. 2. 5. Walker, B. E.: The association of mucopolysaccharides with morphogenesis of the palate and other structures in mouse embryos. J. Embryol. & Exper. Morphol., 9:22, 1961. 6. Walker, B. E., and Fraser, F. C. : Closure of the secondary palate in three strains of mice. J. Embryol. & Exper. Morphol., 4:176, 1956. 7. Runner, M. N.: Inheritance of susceptibility to congenital deformity. Metabolic clues provided by experiments with teratogenic agents. Pediatrics, 23:254, 1959.
EYE COMPLAINTS AS SYMPTOMS O F PSYCHIATRIC DISORDER* J O H N CLANCY,
M.D.
Iowa City, Iowa
The diagnostic and statistical manual, Mental Disorders,1 prepared by the Ameri can Psychiatric Association, contains no special section on psychiatric conditions affecting the eye. It is recognized that emo tional factors may play a causative role in disturbances of many organs and organ systems, and localized complaints are re garded as symptoms of the total reaction of the personality. Functional disturbances are first classified according to type of reaction and secondly as to symptom location. In every-day speech, however, the eye is credited with properties ♦From the Department of Psychiatry, College of Medicine, State University of Iowa.
and behavior which have little to do with its primary function and, for the sake of com pleteness, I have endeavored to classify these "aberrant functions." Three divisions suggested themselves: (1) emotional eyes, (2) behavioristic eyes, (3) miscellaneous eyes. In the first group I included the evil eyes, baleful eyes, green and envious eyes, red and tearful eyes, jaundiced eyes, and so forth. In the second group came the bulging eyes, popping eyes, searching eyes, penetrating eyes, roving eyes, loving eyes and lecherous eyes. The miscellaneous column listed the hungry eyes, the private eyes and bedroom eyes, to name a few. Such an exercise in nonsense at once