"Induction of vascular endothelial growth factor by 4-hydroxynonenal and its prevention by glutathione precursors in retinal
pigment epithelial cells" Surya P. Ayalasomayajula a, Uday B. Kompella a,b,* Department of Pharmaceutical Sciences and ophthalmology, University of Nebraska Medical Center, Omaha, NE 68198-6025, USA
"Oxidative Damage and Protection of the RPE" Jiyang Cai, Kasey C. Nelson, Mei Wu, Paul Sternberg Jr* and Dean P. JonesDepartment of Biochemistry and Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA
Glutathione: a vital lens antioxidant. J Ocul Pharmacol Ther. 2000 Apr;16(2):121-35. Eye Research Institute, Oakland University, Rochester, Michigan 48309-4401, USA
GLUTATHIONE IN HUMAN PLASMA: DECLINE IN ASSOCIATION WITH AGING, AGE-RELATED MACULAR DEGENERATION, AND DIABETES
PAULA S. SAMIEC,*†‡ CAROLYN DREWS-BOTSCH,†§ ELAINE W. FLAGG,§ JOANNE C. KURTZ,*†*Department of Biochemistry,; †Department of Ophthalmology,; ‡Program in Physiology and Pharmacology, School of Medicine, Emory University, Atlanta, GA, USA; and §Division of Epidemiology, School of Public Health, Emory University, Atlanta, GA, USA
Beatty S., 2000. The role of oxidative stress in the pathogenesis of age-related macular degeneration.
Beatty S., 2001. Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population.
Bone RA., 2000. Lutein and zeaxanthin in the eyes, serum and diet of human subjects.
Brown NA., 1998. Nutrition supplements and the eye.
Brubaker RF., 2000. Ascorbic acid content of human corneal epithelium.
Giblin FJ., 2000. Glutathione: a vital lens antioxidant.
Ishihara N., 1997. [Antioxidants and angiogenetic factor associated with age-related macular degeneratio
Kaven C., 2001. Thalidomide and prednisolone inhibit growth factor-induced human retinal pigment epitheliumcell proliferation in vitro.
Landrum JT., 2001. Lutein, zeaxanthin, and the macular pigment.
Lopez Bernal D., 1993. Artificial tear composition and promotion of recovery of the damaged corneal epithelium.
Lutty G., 1999. Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration.
Piovella C., 1973. Effects of ginkgo-biloba on the micro-vessels of bulbar conjunctiva.
Rapp LM., 2000. Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina.
Richer S., 1996. Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2:
antioxidant intervention and conclusions.
Schwartz LH., 1997. [Radiotherapy and age-related macular degeneration: a review of the literature]
Seddon JM., 2001. Dietary fat and risk for advanced age-related macular degeneration.
Seddon JM., 1996. A prospective study of cigarette smoking and age-related macular degeneration in women.
Smith W., 2000. Dietary fat and fish intake and age-related maculopathy.
Specht S., 2000. Continuing damage to rat retinal DNA during darkness following light exposure.
Suggested Reading Abstracts Anon., 1993. Antioxidant status and neovascular age-related macular degeneration. Eye Disease Case-Control Study Group
Baurmann H., 1975. Results of fluorescence angiography of the posterior pole of the eye.
Berkow JW., 1984. Subretinal neovascularization in senile macular degeneration.
Chan D., 1998. Cigarette smoking and age related macular degeneration.
Chong NHV., 1998. Alternative therapies in exudative age related macular degeneration.
Ciulla TA., 1998. Age related macular degeneration : a review of experimental treatments.
Cohen SM., 2000. Low glutathione reductase and peroxidase activity in age-related macular degeneration.
Darzins P., 1997. Sun exposure and age related macular degeneration. An Australian case control study.
De La Paz MA., 1996. Antioxidant enzymes of the human retina: effect of age on enzyme activity of macula and periphery.
Elliott AJ., 1992. Inhibition of glutathione reductase by flavonoids. A structure-activity study.
Frank R.N., 1998. Oxidative protector' enzymes in the macular retinal pigment epithelium of aging eyes andeyes with age related macular degeneration.
Havsteen B., 1983. Flavonoids, a class of natural products of high pharmacological potency.
Ishihara N., 1997. Antioxidants and angiogenetic factor associated with age related macular degeneration(exudative type)]
Jennings PE., 1991. Oxidative effects of laser photocoagulation.
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Lebuisson DA., 1986. [Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminarydouble-blind drug vs. placebo study]
Lietti A., 1976. Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity.
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Morley JE., 1988. Nutrition in the elderly.
Nicolas MG., 1996. Studies on the mechanism of early onset macular degeneration in cynomolgus monkeys. II.
Suppression of metallothionein synthesis in the retina in oxidative stress.
Niesel P., 1977. [Th clinical picture of retinal thrombosis (author's transl)]
Obisesan TO., 1998. Moderate wine consumption is associated with decreased odds of developing age
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Olson RJ., 1998. Zinc as a treatment for age related macular degeneration
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Prashar S., 1993. Antioxidant enzymes in RBCs as a biological index of age related macular degeneration.
Schatz H., 1989. Atrophic macular degeneration. Rate of spread of geographic atrophy and visual loss.Schwartz LH., 1997. Radiotherapy and age related macular degeneration: a review of the literature]
Seddon JM., 1994. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular
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Shukla M., 1989. Hydergine-a new promise in neuro-retinal disorders.
Spital G., 1998. Autofluorescence characteristics of lipofuscin components in different forms of late senile
Starr CE., 1998. Age related macular degeneration. Can we stem this worldwide public health crisis?
Teeters VW., 1973. The development of neovascularization of senile disciform macular degeneration.
Teichmann KD., 1997. Treatment of macular degeneration, according to Bangerter.
Tixier JM., 1984. Evidence by in vivo and in vitro studies that binding of pycnogenols to elastin affects its rate of
degradation by elastases.
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Wallow IH., 1988. Cystoid macular degeneration in experimental branch retinal vein occlusion. Wu LH., 1987. Study of aging macular degeneration in China.
Zhao J., 1995. Delayed macular choriocapillary circulation in age-related macular degeneration.
The role of oxidative stress in the pathogenesis of age-related macular degeneration.
Beatty S, Koh H, Phil M, Henson D, Boulton M. Academic Department of Ophthalmology, Manchester Royal Eye Hospital,
Manchester, United Kingdom.
Surv Ophthalmol 2000 Sep-Oct;45(2):115-34
Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis
remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has
been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and
singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress
because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In
vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant
vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived,
at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the
relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although
a protective effect of high plasma concentrations of alpha-tocopherol has been convincingly demonstrated. Macular pigment is also
believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for
AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color, and
reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin
were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is
enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the
onset and natural course of age-related macular disease is currently being evaluated.
Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population.
Beatty S, Murray IJ, Henson DB, Carden D, Koh H, Boulton ME. University Department of Ophthalmology, Manchester Royal Eye
Hospital, Manchester, UK. email@example.com
Invest Ophthalmol Vis Sci 2001 Feb;42(2):439-46
Lutein and zeaxanthin in the eyes, serum and diet of human subjects.
Bone RA, Landrum JT, Dixon Z, Chen Y, Llerena CM. Department of Physics, Florida International University, Miami, FL 33199,
Exp Eye Res 2000 Sep;71(3):239-45
Inverse associations have been reported between the incidence of advanced, neovascular, age-related macular degeneration (AMD)
and the combined lutein (L) and zeaxanthin (Z) intake in the diet, and L and Z concentration in the blood serum.
Macular pigment in donor eyes with and without AMD: a case-control study.
Bone RA, Landrum JT, Mayne ST, Gomez CM, Tibor SE, Twaroska EE. Department of Physics, Florida International University,
Miami, Florida 33199, USA. firstname.lastname@example.org
Invest Ophthalmol Vis Sci 2001 Jan;42(1):235-40
Photodynamic therapy with verteporfin (Visudyne): impact on ophthalmology and visual sciences.
Bressler, N.M., Bressler, S.B.
Invest. Ophthalmol. Vis. Sci. 2000 Mar; 41(3): 624 8.
No abstract available.
Nutrition supplements and the eye.
Brown NA, Bron AJ, Harding JJ, Dewar HM. Clinical Cataract Research Unit, Nuffield Laboratory of Ophthalmology, Oxford, UK.
Eye 1998;12 ( Pt 1):127-33
Ascorbic acid content of human corneal epithelium.
Brubaker RF, Bourne WM Bachman LA, McLaren JW. Department of Ophthalmology, Mayo Clinic and Mayo Foundation,
Rochester, Minnesota 55905, USA. email@example.com
Invest Ophthalmol Vis Sci 2000 Jun;41(7):1681-3
Glutathione: a vital lens antioxidant.
Giblin FJ. Eye Research Institute, Oakland University, Rochester, Michigan 48309-4401, USA.
J Ocul Pharmacol Ther 2000 Apr;16(2):121-35
The reducing compound glutathione (GSH) exists in an unusually high concentration in the lens where it functions as an essential antioxidant vital for maintenance of the tissue's transparency. In conjunction with an active glutathione redox cycle located in the lens epithelium and superficial cortex, GSH detoxifies potentially damaging oxidants such as H2O2 and dehydroascorbic acid.
Recent studies have indicated an important hydroxyl radical-scavenging function for GSH in lens epithelial cells, independent of the cells' ability to detoxify H2O2. Depletion of GSH or inhibition of the redox cycle allows low levels of oxidant to damage lens epithelial targets such as Na/K-ATPase, certain cytoskeletal proteins and proteins associated with normal membrane permeability. The level of GSH in the nucleus of the lens is relatively low, particularly in the aging lens, and exactly how the compound travels from the epithelium to the central region of the organ is not known. Recently, a cortical/nuclear barrier to GSH migration in older huma lenses was demonstrated by Sweeney et al. The relatively low ratio of GSH to protein -SH in the nucleus of the lens, combined with low activity of the glutathione redox cycle in this region, makes the nucleus especially vulnerable to oxidative stress, as has been demonstrated with use of in vivo experimental animal models such as hyperbaric oxygen, UVA light and the glutathione peroxidase knockout mouse. Effects observed in these models, which are currently being utilized to investigate the mechanism of formation of human senile nuclear cataract, include an increase in lens nuclear disulfide, damage to nuclear membranes and an increase in nuclear light scattering. A need exists for development of therapeutic agents to slow age-related loss of antioxidant activity in the nucleus of the human lens to delay the onset of cataract.
[Antioxidants and angiogenetic factor associated with age-related macular degeneration (exudative type)]
Ishihara N; Yuzawa M; Tamakoshi A Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.
Nippon Ganka Gakkai Zasshi (Japan) Mar 1997, 101 (3) p248-51
Lutein, zeaxanthin, and the macular pigment.
Landrum JT, Bone RA. Department of Chemistry, Florida International University, Miami 33199, USA.
Arch Biochem Biophys 2001 Jan 1;385(1):28-40
The predominant carotenoids of the macular pigment are lutein, zeaxanthin, and meso-zeaxanthin. The regular distribution pattern of these carotenoids within the human macula indicates that their deposition is actively controlled in this tissue. The chemical, structural, and optical characteristics of these carotenoids are described. Evidence for the presence of minor carotenoids in the retina is cited. Studies of the dietary intake and serum levels of the xanthophylls are discussed. Increased macular carotenoid levels result from supplementation of humans with lutein and zeaxanthin. A functional role for the macular pigment in protection against light-induced retinal damage and age-related macular degeneration is discussed. Prospects for future research in the study of macular pigment require new initiatives that will probe more accurately into the localization of these carotenoids in the retina, identify possible transport proteins and mechanisms, and prove the veracity of the photoprotection hypothesis for the macular pigments.
Effects of ginkgo-biloba on the micro-vessels of bulbar conjunctiva.
Piovella, C. Minerva Med. 1973 Nov 7; 64(79, Suppl.): 4179-86 (in Italian).
Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2: antioxidant intervention and conclusions.
Richer S. Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064, USA.
J Am Optom Assoc 1996 Jan;67(1):30-49
Dietary fat and risk for advanced age-related macular degeneration.
Seddon JM, Rosner B, Sperduto RD, Yannuzzi L, Haller JA, Blair NP, Willett W. Epidemiology Unit, Department of Ophthalmology,
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. Johanna_Seddon@meei.harvard.edu
Arch Ophthalmol 2001 Aug;119(8):1191-9
Dietary fat and fish intake and age-related maculopathy.
Smith W, Mitchell P, Leeder SR. National Centre for Epidemiology and Population Health, Australian National University, Australian
Capital Territory. firstname.lastname@example.org
Arch Ophthalmol 2000 Mar;118(3):401-4
Antioxidant status and neovascular age-related macular degeneration. Eye Disease Case-Control Study Group.
Anon. [No authors listed]
Arch Ophthalmol. 1993 Jan;111(1):104-9.
Age related macular degeneration : a review of experimental treatments.
Ciulla TA; Danis RP; Harris A Indiana University Macular Degeneration Clinic and Research Center, Department of Ophthalmology,
Indiana University School of Medicine, Indianapolis, USA.
Surv Ophthalmol (Netherlands) Sep Oct 1998, 43 (2) p134 46
. Laser treatment of drusen is being evaluated as a means of limiting the risk of CNVM formation,
although mixed results have been reported in the small number of studies to date. Choroidal perfusion abnormalities have been
described in AMD, and some investigators postulate that altering blood flow may limit the risk of CNVM formation. No perfusion
treatment trials have been completed to date. (183 Refs.)
Low glutathione reductase and peroxidase activity in age-related macular degeneration.
Cohen SM, Olin KL, Feuer WJ, Hjelmeland L, Keen CL, Morse LS. Department of Ophthalmology, University of California, Davis,
Br J Ophthalmol. 1994 Oct;78(10):791-4.
Antioxidant enzymes of the human retina: effect of age on enzyme activity of macula and periphery.
De La Paz MA, Zhang J, Fridovich I. Duke University Eye Center, DUMC, Durham, NC 27710, USA.
Curr Eye Res. 1996 Mar;15(3):273-8.
Inhibition of glutathione reductase by flavonoids. A structure-activity study.
Elliott AJ, Scheiber SA, Thomas C, Pardini RS. Allie M. Lee Laboratory for Cancer Research, Department of Biochemistry,
University of Nevada, Reno 89557.
Biochem Pharmacol. 1992 Oct 20;44(8):1603-8.
Oxidative protector' enzymes in the macular retinal pigment epithelium of aging eyes and eyes with age related macular degeneration
Frank R.N. Dr. R.N. Frank, Kresge Eye Institute, Wayne State Univ. Sch. of Medicine, Detroit, MI United States
Trans. of the Am. Ophthalmol. Soc. 1998, 96/ (635 689)
Flavonoids, a class of natural products of high pharmacological potency.
Genetic association of apolipoprotein E with age related macular degeneration.
Klaver CC; Kliffen M; van Duijn CM; Hofman A; Cruts M; Grobbee DE; van Broeckhoven C; de Jong PT Department of Epidemiology,
Erasmus University Medical School, Rotterdam, The Netherlands.
Am J Hum Genet (United States) Jul 1998, 63 (1) p200 6
Age related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD.
[Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary double-blind drug vs. placebo Lebuisson DA, Leroy L, Rigal G. Presse Med. 1986 Sep 25;15(31):1556-8.
Antioxidant enzymes in RBCs as a biological index of age related macular degeneration. Prashar S, Pandav SS, Gupta A, Nath R. Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.Acta Ophthalmol (Copenh). 1993 Apr;71(2):214-8.
Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group.
Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT, et al. Epidemiology
Unit, Massachusetts Eye and Ear Infirmary, Boston 02114.
JAMA. 1994 Nov 9;272(18):1413-20.
RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD,
CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.
[Antioxidants for prophylaxis of eye diseases]
Klin Oczna (Poland) Feb 1996, 98 (2) p141-3
The contemporary literature has widely described the role of free oxygen radicals and their antioxidants in pathogenesis of some eye diseases, mainly cataract, age-related macular degeneration, retinopathy of prematurity and cystic macular oedema. This paper presents publications which stress the importance of antioxidants use in prophylaxis of cataract and age-related macular degeneration. Positive antioxidants role was proved both in experimental research and in clinical observations. (29 Refs.)
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston MA 02114, USA.
Vision Res (England) Sep 1996, 36 (18) p3003-9
Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group
Antioxidant enzymes of the human retina: Effect of age on enzyme activity of macula and periphery
De La Paz M.A.; Zhang J.; Fridovich I.
Duke University Eye Center, DUMC, Box 3802, Durham, NC 27710 USA
Current Eye Research (United Kingdom), 1996, 15/3 (273-278)