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Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment
LABORATORY SCIENCE
Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment Line Kessel, MD, PhD, Jesper Holm Lundeman, PhD, Kristina Herbst, MD, Thomas Vestergaard Andersen, PhD, Michael Larsen, DrMedSci
PURPOSE: To characterize age-related changes in the transmission of light through noncataractous human lenses. SETTING: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark. METHODS: The spectral transmission of white light was measured along the visual axis in the most central part of the lens in vitro in intact human donor lenses over a wide range of ages. RESULTS: The study evaluated 28 intact human donor lenses of 15 donors aged 18 to 76 years. Increasing age was associated with gradually decreasing transmission at all visible wavelengths, most prominently at shorter wavelengths. Empirical formulas describing the age-related loss of transmission were created for each spectral color. At 480 nm, the absorption peak for melanopsin, transmission decreased by 72% from the age of 10 years to the age of 80 years. CONCLUSION: The age-related decrease in spectral transmission through the human lens could be modeled by a simple algorithm that may be useful in the design of intraocular lenses that mimic the characteristics of the human lens and in studies of color vision, psychophysics, and melanopsin activation. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2010; 36:308–312 Q 2010 ASCRS and ESCRS
Visual function depends on the quality of the image formed on the retina and the ability of the retina to register and transmit this image to the brain. Globally, deteriorating optical quality of the lens is the leading cause of blindness and severe visual loss.1 The condition is termed cataract when it reaches a level of functional significance. Cataract formation involves changes in the protein–protein interaction2 caused by posttranslational modifications of lens proteins. These spontaneous degradative modifications accumulate during the life span of the individual3,4 because there is no removal of damaged proteins from the lens.5 Cataract is treated by surgically removing the content of the capsular lens bag and replacing it with an artificial lens; that is, an intraocular lens (IOL). Firstgeneration IOLs were transparent even to ultraviolet (UV) radiation,6 whereas modern IOLs block the transmission of UV radiation to protect the retina from phototoxic damage. Because the action spectrum for retinal phototoxicity extends into the blue end of the 308
Q 2010 ASCRS and ESCRS Published by Elsevier Inc.
visible region,7,8 IOLs that block the transmission of blue light were recently introduced on the market. These IOLs are tinted a yellow that is intended to mimic the yellow of the aged human lens to offer a degree of intrinsic protection against retinal damage. Attention to this grew after the publication of reports suggesting that the rate of progression of age-related macular degeneration increases after cataract surgery.9 An important argument against the use of blue light–filtering IOLs is that they may interfere with the entrainment of the circadian rhythm by inhibiting the stimulation of melanopsin-containing ganglion cells in the retina.10 Whereas the retinal phototoxicity of short-wavelength light has been well documented in animal experiments,7,8 the relevance of the findings to human studies is difficult to assess because the animals generally are younger than 1 year and have clear, colorless lenses. As a consequence, the spectral transmission of the human lens at a given age should be taken into 0886-3350/10/$dsee front matter doi:10.1016/j.jcrs.2009.08.035
LABORATORY SCIENCE: TRANSMISSION PROPERTIES OF THE HUMAN LENS
account when animal studies are extrapolated to human studies. Previous studies of the spectral characteristics of human lenses are limited by the small number of lenses studied,11 the spectral range reported,12,13 a limited age range,14 restriction of studies to a part of the lens,15 and the use of frozen lenses.16 The aim of the present study was to characterize the spectral changes in the transmission properties of the human lens as a function of age. MATERIALS AND METHODS Human Donor Lenses Human donor lenses provided by the CorneaBank NORI, Amsterdam, The Netherlands, and the Lions Eye Institute for Transplant and Research, Tampa, Florida, USA, were received and maintained in transport medium (minimum essential medium or Optisol GS). The type of transport medium had no detectable effect on the transmission properties of the lens.
Transmission Measurement The transmission of visible and near-infrared light (400 mm to 800 nm) was studied with the intact lenses placed in 5.0 mm path length quartz cuvettes (Starna Scientific, Ltd.) filled with a neutral saline solution containing (in g/L) 8.00 sodium chloride, 0.40 potassium chloride, 0.10 disodium hydrogen phosphate, 1.00 glucose, and 2.38 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPE) buffered with sodium hydroxide to a pH of 7.4.17 The transmission was calculated as the ratio of the intensity of white light transmitted by a human lens compared with the transmission of light by a blank quartz cuvette filled with the saline solution subtracting the background level of light as follows: Spectrumlens Spectrumbackground TransmissionZ Spectrumcuvette Spectrumbackground
(1)
Submitted: July 16, 2009. Final revision submitted: August 17, 2009. Accepted: August 19, 2009. From the Department of Ophthalmology (Kessel, Lundeman, Herbst, Larsen), Glostrup Hospital, University of Copenhagen, and Koheras A/S (Andersen), Birkerød, Denmark..
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The transmission was measured through the axial portion of the lens (G0.5 mm from its anatomical axis) with the anterior side facing the light source. A super-continuum white-light source (SuperK Blue, Koheras A/S) was used, producing a collimated beam of light from 395 to 2100 nm with a beam diameter of approximately 1.0 mm. After passing through the cuvette containing the human lens, the light was collected by an integrating sphere (FOIS-1) coupled to a spectrometer (USB4000) by an optical fiber (P600-2-UV-VIS.) and controlled by a computer program (Spectra Suite) (all Ocean Optics, Inc.) (Figure 1). The collection of light by an integrating sphere was chosen because the chromatic and spectral aberrations by the human lens have a significant effect on the transmission characteristics of the lens due to differences in in-coupling depending on the exact positioning of the lens when a fiber based–only system is used. The transmission of white light was measured through 2 IOLs using the same setup used for the human donor lenses except that the IOLs were sandwiched between 2 glass microscope mounting plates and covered with a 2.0 mm circular aperture, exposing only the most central 2.0 mm of the IOL to the illumination light source. The 2 IOLs were a 20.0 diopter (D) AcrySof IQ SN60WF blue-light filtering and a 20.0 D AcrySof Natural SA60AT UV blocking (both Alcon, Inc.). All statistical analyses were performed using the SAS software (version 9.1, SAS Institute, Inc.). The level of statistical significance was set at 0.05.
RESULTS Twenty-eight lenses of 15 donors were examined. The age of the donors ranged from 18 to 76 years. Older lenses were thicker, had a larger diameter, and were more densely yellow than younger lenses but with interindividual variations that were related to systemic health factors (Figure 2). Lenses from donors with a history of diabetes mellitus were markedly larger and with more dense yellow discoloration. The individual variations in color were also reflected in the recordings of the transmission properties. In general, transmission spectra showed a monotonous decrease in transmission from the red to the blue end of the spectrum with age (Figure 3). The transmission was modeled as a linear function of age for each of the 7 spectral bands, which are indicted by color names (Table 1 and Figure 4). Light
Supported by the National Danish Research Council (Forskningsra˚det for Sundhed og Sygdom, grant 271-06-0664) and the National Danish Advanced Science Foundation (Højteknologifondet), Copenhagen, Denmark. Liesbeth Pels, PhD, CorneaBank NORI, Amsterdam, The Netherlands, and Nicholas Sprehe, Lions Eye Institute for Transplant and Research, Tampa, Florida, USA, provided assistance. Corresponding author: Line Kessel, MD, PhD, Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Nordre Ringvej 57, DK-2600 Glostrup, Denmark. E-mail: linkes01@glo. regionh.dk.
Figure 1. Experimental setup for measurement of light transmission in human lenses in vitro. A broadband coherent light source (right) emits a collimated beam of white light. After passing through the lens, the light is collected by an integrating sphere connected to a spectrometer by an optical fiber.
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Figure 2. Photographs of 6 human donor lenses aged 18 years, 21 years, and 46 years (upper row, left to right) and 62 years, 73 years, and 76 years (lower row, left to right). The donors aged 62 and 76 years had a history of diabetes mellitus, and their lenses are larger and more densely yellow than that of the 73-year-old donor. The dark areas on the 2 youngest lenses are adhering iris pigment.
transmission for all colors decreased significantly with age, although the effect of age was greatest for shorter wavelengths, with age accounting for 92% of the variation in transmission of violet light but 13% of the variation in transmission of red light. For violet light, the transmission ranged from 44% in a 10-year-old lens to 1% in an 80-year-old lens. The transmission of red light was high at all ages, ranging from 87% in a 10-year-old lens to 79% in an 80-year-old lens. The violet and blue parts of the spectrum were most prominently affected by age (Table 1 and Figure 5). This is the part of the spectrum at which photoentrainment is stimulated via the stimulation of melanopsin in a subset of retinal ganglion cells. Melanopsin has an absorption peak at 480 nm. The transmission at 480 nm was 82% in a 10-year-old lens, decreasing to 56% in a 40-year-old lens and 23% in an 80-year-old
lens. Thus, the stimulation of melanopsin can be predicted to decrease by 72% from the age of 10 years to the age of 80 years. Figure 5 also shows the transmission curves of the UV-blocking IOL and blue light–filtering IOL. The blue light–filtering IOL also blocked part of the spectral region for melanopsin stimulation, but not to the same extent as the natural aged lens. DISCUSSION The present study provides data enabling modeling of the spectral transmission of the human lens as a function of age. The results may be useful in various applications, such as retinal light dosimetry during therapeutic light exposure and in psychophysical examinations or in setting the dose of experimental phototherapy of winter depression.
Table 1. Age-related changes in the transmission of light through human donor lenses. Color Violet (400–449 nm) Blue (450–489 nm) Green (490–559 nm) Yellow (560–589 nm) Orange (590–629 nm) Red (630–699 nm) Near infrared (700–800 nm)
Figure 3. Spectral transmission in vitro of human donor lenses aged 18, 21, 46, 62, 73, and 76 years (same lenses as in Figure 2).
Slope (a) Intercept (b) P Value r Value 0.6 0.8 0.5 0.3 0.2 0.1 0.1
50.1 82.9 88.3 88.8 89.4 90.0 92.6
!.0001 !.0001 !.0001 .0007 .0092 .064 .0147
0.92 0.81 0.61 0.37 0.23 0.13 0.24
Parameters of the linear regression model (Transmission Z b a Age) of light transmission in the human lens at various wavelengths (see also Figure 4)
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Figure 4. Lens transmission in vitro in selected spectral bands for 28 human lenses with regression curves (see Table 1) describing the mean reduction in transmission with age. The color of the lines and the markers indicate the following spectral bands: violet (400 to 449 nm), blue (450 to 489 nm), green (490 to 559 nm), yellow (560 to 589 nm), orange (590 to 629 nm), red (630 to 699 nm), and infrared (700 to 800 nm) (IR Z infrared).
Figure 5. Model curves of transmission in the human lens at ages 20 to 70 years relative to the transmission of a 10-year-old lens. The absorption curve of melanopsin is also shown (redrawn from Hankins et al.18) to show the predilection for age-related transmission loss to affect the blue end of the visible spectrum, where the melanopsin photopigment is stimulated. For comparison, the transmission curves of a 20.0 D UV-blocking IOL and a 20.0 D blue light–blocking IOL are shown (UV Z ultraviolet).
The young lens is highly transparent to all visible wavelengths; however, transmission decreases significantly after 30 years of age, especially in the violet and blue region of the spectrum. Although the accumulation of yellow chromophores is responsible for the preferential loss of light transmission in the blue end of the spectrum, it is not in itself a cause of loss of visual acuity; however, it reduces the ability to perceive and distinguish shades of blue.18 Hypothetically, decreased transmission of blue light by the aging lens, through depressed activation of melanopsin, may be responsible for the increased risk for depression and sleep disorders in the elderly population.19,20 Melanopsin is a photosensitive pigment that is important for circadian photoentrainment by stimulating melatonin secretion by the pineal gland.21,22 It is expressed in a small subset of retinal ganglion cells. It has an absorption maximum near 480 nm and is active only in bright light.23–25 The quality, quantity, and architecture of sleep are affected by age,26 and cataract surgery improves sleep.20 Thus, dim light and reduced transmission of blue light have a major impact on the circadian pace, sleep disorders, and mental mood,27 and the results in the present study show that age-induced yellowing of the human lens is responsible for the changes in sleep with age. In conclusion, we propose that our quantitative model of spectral light transmission in the human lens may provide new quantitative measures of lens transmission to assist in the study of the activation of melanopsin and the retinohypothalamic tract and in the design of new IOLs that mimic the retinoprotective effects of the aged human lens without compromising circadian entrainment.
REFERENCES 1. Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP. Global data on visual impairment in the year 2002. Bull World Health Organ 2004; 82:844–851. Available at: http://www.who.int/bulletin/volumes/82/11/en/844arabic.pdf. Accessed November 8, 2009 2. Takemoto L, Sorensen CM. Protein-protein interactions and lens transparency. Exp Eye Res 2008; 87:496–501 3. Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C, Tardieu A. Ageing and vision: structure, stability and function of lens crystallins. Prog Biophys Mol Biol 2004; 86:407–485 4. Horwitz J. The function of alpha-crystallin in vision. Semin Cell Dev Biol 2000; 11:53–60 5. Lynnerup N, Kjeldsen H, Heegaard S, Jacobsen C, Heinemeier J. Radiocarbon dating of the human eye lens crystallines reveal proteins without carbon turnover throughout life. PLoS ONE 2008; 3(1):e1529. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2211393/pdf/pone.0001529.pdf. Accessed November 8, 2009 6. Mainster MA. Spectral transmittance of intraocular lenses and retinal damage from intense light sources. Am J Ophthalmol 1978; 85:167–170 7. Ham WT Jr, Mueller HA, Sliney DH. Retinal sensitivity to damage from short wavelength light [letter]. Nature 1976; 260:153–155 8. Gorgels TGMF, van Norren D. Ultraviolet and green light cause different types of damage in rat retina. http://www.iovs.org/cgi/ reprint/36/5/851. Available atAccessed November 8, 2009 9. Bockelbrink A, Roll S, Ruether K, Rasch A, Greiner W, Willich SN. Cataract surgery and the development or progression of age-related macular degeneration: a systematic review. Surv Ophthalmol 2008; 53:359–367 10. Mainster MA. Violet and blue light blocking intraocular lenses: photoprotection versus photoreception. http://www.pubmedcentral. nih.gov/picrender.fcgi?artid. Available at:Z 1860240&blobtype Z pdf Accessed November 8, 2009 11. Boettner EA, Wolter JR. Transmission of the ocular media. http://www.iovs.org/cgi/reprint/1/6/776. Available at: Accessed November 8, 2009 12. Weale RA. Age and the transmittance of the human crystalline lens. http://jp.physoc.org/cgi/reprint/395/1/577. Available at: Accessed November 8, 2009
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13. Dillon J, Zheng L, Merriam JC, Gaillard ER. Transmission of light to the aging human retina: possible implications for age related macular degeneration. Exp Eye Res 2004; 79:753–759 14. Lei B, Yao G. Spectral attenuation of the mouse, rat, pig and human lenses from wavelengths 360 nm to 1020 nm. Exp Eye Res 2006; 83:610–614 15. Nishimoto K, Sasaki K. In vivo light scattering intensity in the lens versus in vitro spectral transmission in the nuclear region. Ophthalmic Res 1995; 27:1–11 16. Lerman S, Borkman R. Spectroscopic evaluation and classification of the normal, aging, and cataractous lens. Ophthalmic Res 1976; 8:335–353 17. Glasser A, Campbell MCW. Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia. Vision Res 1999; 39:1991–2015 18. Kessel L, Alsing A, Larsen M. Diabetic versus non-diabetic colour vision after cataract surgery. http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC1723195/pdf/v083p01042.pdf. Available at: Accessed November 8, 2009 19. Hollwich F, Dieckhues B. Der Einfluß des Lichtes u¨ber das Auge auf den Stoffwechsel und die Hormone. [The influence of light via the eye on metabolism and hormones]. Klin Monatsbl Augenheilkd 1989; 195:284–290 20. Asplund R, Ejdervik Lindblad B. Sleep and sleepiness 1 and 9 months after cataract surgery. Arch Gerontol Geriatr 2004; 38:69–75 21. Hattar S, Liao H-W, Takao M, Berson DM, Yau K- W. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 2002; 295:1065–1070 22. Hankins MW, Peirson SN, Foster RG. Melanopsin: an exciting photopigment. Trends Neurosci 2008; 31:27–36
23. Dacey DM, Liao H-W, Peterson BB, Robinson FR, Smith VC, Pokorny J, Yau K-W, Gamlin PD. Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN [letter]. Nature 2005; 433:749–754 24. Hattar S, Lucas RJ, Mrosovsky N, Thompson S, Douglas RH, Hankins MW, Lem J, Biel M, Hofmann F, Foster RG, Yau KW. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice [letter]. Nature 2003; 424:76–81 25. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science 2002; 295:1070–1073 26. Espiritu JRD. Aging-related sleep changes. Clin Geriatr Med 2008; 24(1):1–14; v 27. Zeitzer JM, Dijk D-J, Kronauer RE, Brown EN, Czeisler CA. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. J Physiol(526): 695–702. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270041/ pdf/tjp0526-0695.pdf. Available at: Accessed November 8, 2009
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First author: Line Kessel, MD, PhD Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark
Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment Line Kessel, MD, PhD, Jesper Holm Lundeman, PhD, Kristina Herbst, MD, Thomas Vestergaard Andersen, PhD, Michael Larsen, DrMedSci
PURPOSE: To characterize age-related changes in the transmission of light through noncataractous human lenses. SETTING: Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark. METHODS: The spectral transmission of white light was measured along the visual axis in the most central part of the lens in vitro in intact human donor lenses over a wide range of ages. RESULTS: The study evaluated 28 intact human donor lenses of 15 donors aged 18 to 76 years. Increasing age was associated with gradually decreasing transmission at all visible wavelengths, most prominently at shorter wavelengths. Empirical formulas describing the age-related loss of transmission were created for each spectral color. At 480 nm, the absorption peak for melanopsin, transmission decreased by 72% from the age of 10 years to the age of 80 years. CONCLUSION: The age-related decrease in spectral transmission through the human lens could be modeled by a simple algorithm that may be useful in the design of intraocular lenses that mimic the characteristics of the human lens and in studies of color vision, psychophysics, and melanopsin activation. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2010; 36:308–312 Q 2010 ASCRS and ESCRS
Visual function depends on the quality of the image formed on the retina and the ability of the retina to register and transmit this image to the brain. Globally, deteriorating optical quality of the lens is the leading cause of blindness and severe visual loss.1 The condition is termed cataract when it reaches a level of functional significance. Cataract formation involves changes in the protein–protein interaction2 caused by posttranslational modifications of lens proteins. These spontaneous degradative modifications accumulate during the life span of the individual3,4 because there is no removal of damaged proteins from the lens.5 Cataract is treated by surgically removing the content of the capsular lens bag and replacing it with an artificial lens; that is, an intraocular lens (IOL). Firstgeneration IOLs were transparent even to ultraviolet (UV) radiation,6 whereas modern IOLs block the transmission of UV radiation to protect the retina from phototoxic damage. Because the action spectrum for retinal phototoxicity extends into the blue end of the 308
Q 2010 ASCRS and ESCRS Published by Elsevier Inc.
visible region,7,8 IOLs that block the transmission of blue light were recently introduced on the market. These IOLs are tinted a yellow that is intended to mimic the yellow of the aged human lens to offer a degree of intrinsic protection against retinal damage. Attention to this grew after the publication of reports suggesting that the rate of progression of age-related macular degeneration increases after cataract surgery.9 An important argument against the use of blue light–filtering IOLs is that they may interfere with the entrainment of the circadian rhythm by inhibiting the stimulation of melanopsin-containing ganglion cells in the retina.10 Whereas the retinal phototoxicity of short-wavelength light has been well documented in animal experiments,7,8 the relevance of the findings to human studies is difficult to assess because the animals generally are younger than 1 year and have clear, colorless lenses. As a consequence, the spectral transmission of the human lens at a given age should be taken into 0886-3350/10/$dsee front matter doi:10.1016/j.jcrs.2009.08.035
LABORATORY SCIENCE: TRANSMISSION PROPERTIES OF THE HUMAN LENS
account when animal studies are extrapolated to human studies. Previous studies of the spectral characteristics of human lenses are limited by the small number of lenses studied,11 the spectral range reported,12,13 a limited age range,14 restriction of studies to a part of the lens,15 and the use of frozen lenses.16 The aim of the present study was to characterize the spectral changes in the transmission properties of the human lens as a function of age. MATERIALS AND METHODS Human Donor Lenses Human donor lenses provided by the CorneaBank NORI, Amsterdam, The Netherlands, and the Lions Eye Institute for Transplant and Research, Tampa, Florida, USA, were received and maintained in transport medium (minimum essential medium or Optisol GS). The type of transport medium had no detectable effect on the transmission properties of the lens.
Transmission Measurement The transmission of visible and near-infrared light (400 mm to 800 nm) was studied with the intact lenses placed in 5.0 mm path length quartz cuvettes (Starna Scientific, Ltd.) filled with a neutral saline solution containing (in g/L) 8.00 sodium chloride, 0.40 potassium chloride, 0.10 disodium hydrogen phosphate, 1.00 glucose, and 2.38 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPE) buffered with sodium hydroxide to a pH of 7.4.17 The transmission was calculated as the ratio of the intensity of white light transmitted by a human lens compared with the transmission of light by a blank quartz cuvette filled with the saline solution subtracting the background level of light as follows: Spectrumlens Spectrumbackground TransmissionZ Spectrumcuvette Spectrumbackground
(1)
Submitted: July 16, 2009. Final revision submitted: August 17, 2009. Accepted: August 19, 2009. From the Department of Ophthalmology (Kessel, Lundeman, Herbst, Larsen), Glostrup Hospital, University of Copenhagen, and Koheras A/S (Andersen), Birkerød, Denmark..
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The transmission was measured through the axial portion of the lens (G0.5 mm from its anatomical axis) with the anterior side facing the light source. A super-continuum white-light source (SuperK Blue, Koheras A/S) was used, producing a collimated beam of light from 395 to 2100 nm with a beam diameter of approximately 1.0 mm. After passing through the cuvette containing the human lens, the light was collected by an integrating sphere (FOIS-1) coupled to a spectrometer (USB4000) by an optical fiber (P600-2-UV-VIS.) and controlled by a computer program (Spectra Suite) (all Ocean Optics, Inc.) (Figure 1). The collection of light by an integrating sphere was chosen because the chromatic and spectral aberrations by the human lens have a significant effect on the transmission characteristics of the lens due to differences in in-coupling depending on the exact positioning of the lens when a fiber based–only system is used. The transmission of white light was measured through 2 IOLs using the same setup used for the human donor lenses except that the IOLs were sandwiched between 2 glass microscope mounting plates and covered with a 2.0 mm circular aperture, exposing only the most central 2.0 mm of the IOL to the illumination light source. The 2 IOLs were a 20.0 diopter (D) AcrySof IQ SN60WF blue-light filtering and a 20.0 D AcrySof Natural SA60AT UV blocking (both Alcon, Inc.). All statistical analyses were performed using the SAS software (version 9.1, SAS Institute, Inc.). The level of statistical significance was set at 0.05.
RESULTS Twenty-eight lenses of 15 donors were examined. The age of the donors ranged from 18 to 76 years. Older lenses were thicker, had a larger diameter, and were more densely yellow than younger lenses but with interindividual variations that were related to systemic health factors (Figure 2). Lenses from donors with a history of diabetes mellitus were markedly larger and with more dense yellow discoloration. The individual variations in color were also reflected in the recordings of the transmission properties. In general, transmission spectra showed a monotonous decrease in transmission from the red to the blue end of the spectrum with age (Figure 3). The transmission was modeled as a linear function of age for each of the 7 spectral bands, which are indicted by color names (Table 1 and Figure 4). Light
Supported by the National Danish Research Council (Forskningsra˚det for Sundhed og Sygdom, grant 271-06-0664) and the National Danish Advanced Science Foundation (Højteknologifondet), Copenhagen, Denmark. Liesbeth Pels, PhD, CorneaBank NORI, Amsterdam, The Netherlands, and Nicholas Sprehe, Lions Eye Institute for Transplant and Research, Tampa, Florida, USA, provided assistance. Corresponding author: Line Kessel, MD, PhD, Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Nordre Ringvej 57, DK-2600 Glostrup, Denmark. E-mail: linkes01@glo. regionh.dk.
Figure 1. Experimental setup for measurement of light transmission in human lenses in vitro. A broadband coherent light source (right) emits a collimated beam of white light. After passing through the lens, the light is collected by an integrating sphere connected to a spectrometer by an optical fiber.
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Figure 2. Photographs of 6 human donor lenses aged 18 years, 21 years, and 46 years (upper row, left to right) and 62 years, 73 years, and 76 years (lower row, left to right). The donors aged 62 and 76 years had a history of diabetes mellitus, and their lenses are larger and more densely yellow than that of the 73-year-old donor. The dark areas on the 2 youngest lenses are adhering iris pigment.
transmission for all colors decreased significantly with age, although the effect of age was greatest for shorter wavelengths, with age accounting for 92% of the variation in transmission of violet light but 13% of the variation in transmission of red light. For violet light, the transmission ranged from 44% in a 10-year-old lens to 1% in an 80-year-old lens. The transmission of red light was high at all ages, ranging from 87% in a 10-year-old lens to 79% in an 80-year-old lens. The violet and blue parts of the spectrum were most prominently affected by age (Table 1 and Figure 5). This is the part of the spectrum at which photoentrainment is stimulated via the stimulation of melanopsin in a subset of retinal ganglion cells. Melanopsin has an absorption peak at 480 nm. The transmission at 480 nm was 82% in a 10-year-old lens, decreasing to 56% in a 40-year-old lens and 23% in an 80-year-old
lens. Thus, the stimulation of melanopsin can be predicted to decrease by 72% from the age of 10 years to the age of 80 years. Figure 5 also shows the transmission curves of the UV-blocking IOL and blue light–filtering IOL. The blue light–filtering IOL also blocked part of the spectral region for melanopsin stimulation, but not to the same extent as the natural aged lens. DISCUSSION The present study provides data enabling modeling of the spectral transmission of the human lens as a function of age. The results may be useful in various applications, such as retinal light dosimetry during therapeutic light exposure and in psychophysical examinations or in setting the dose of experimental phototherapy of winter depression.
Table 1. Age-related changes in the transmission of light through human donor lenses. Color Violet (400–449 nm) Blue (450–489 nm) Green (490–559 nm) Yellow (560–589 nm) Orange (590–629 nm) Red (630–699 nm) Near infrared (700–800 nm)
Figure 3. Spectral transmission in vitro of human donor lenses aged 18, 21, 46, 62, 73, and 76 years (same lenses as in Figure 2).
Slope (a) Intercept (b) P Value r Value 0.6 0.8 0.5 0.3 0.2 0.1 0.1
50.1 82.9 88.3 88.8 89.4 90.0 92.6
!.0001 !.0001 !.0001 .0007 .0092 .064 .0147
0.92 0.81 0.61 0.37 0.23 0.13 0.24
Parameters of the linear regression model (Transmission Z b a Age) of light transmission in the human lens at various wavelengths (see also Figure 4)
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Figure 4. Lens transmission in vitro in selected spectral bands for 28 human lenses with regression curves (see Table 1) describing the mean reduction in transmission with age. The color of the lines and the markers indicate the following spectral bands: violet (400 to 449 nm), blue (450 to 489 nm), green (490 to 559 nm), yellow (560 to 589 nm), orange (590 to 629 nm), red (630 to 699 nm), and infrared (700 to 800 nm) (IR Z infrared).
Figure 5. Model curves of transmission in the human lens at ages 20 to 70 years relative to the transmission of a 10-year-old lens. The absorption curve of melanopsin is also shown (redrawn from Hankins et al.18) to show the predilection for age-related transmission loss to affect the blue end of the visible spectrum, where the melanopsin photopigment is stimulated. For comparison, the transmission curves of a 20.0 D UV-blocking IOL and a 20.0 D blue light–blocking IOL are shown (UV Z ultraviolet).
The young lens is highly transparent to all visible wavelengths; however, transmission decreases significantly after 30 years of age, especially in the violet and blue region of the spectrum. Although the accumulation of yellow chromophores is responsible for the preferential loss of light transmission in the blue end of the spectrum, it is not in itself a cause of loss of visual acuity; however, it reduces the ability to perceive and distinguish shades of blue.18 Hypothetically, decreased transmission of blue light by the aging lens, through depressed activation of melanopsin, may be responsible for the increased risk for depression and sleep disorders in the elderly population.19,20 Melanopsin is a photosensitive pigment that is important for circadian photoentrainment by stimulating melatonin secretion by the pineal gland.21,22 It is expressed in a small subset of retinal ganglion cells. It has an absorption maximum near 480 nm and is active only in bright light.23–25 The quality, quantity, and architecture of sleep are affected by age,26 and cataract surgery improves sleep.20 Thus, dim light and reduced transmission of blue light have a major impact on the circadian pace, sleep disorders, and mental mood,27 and the results in the present study show that age-induced yellowing of the human lens is responsible for the changes in sleep with age. In conclusion, we propose that our quantitative model of spectral light transmission in the human lens may provide new quantitative measures of lens transmission to assist in the study of the activation of melanopsin and the retinohypothalamic tract and in the design of new IOLs that mimic the retinoprotective effects of the aged human lens without compromising circadian entrainment.
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First author: Line Kessel, MD, PhD Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark