Etiopathogenesis of non-exudative age-related macular degeneration (literature review)
https://doi.org/10.29413/ABS.2022-7.1.12
Abstract
The article presents an overview of modern publications on epidemiology, risk factors, and the main links of the etiology and pathogenesis of age-related macular degeneration (AMD). The nonexudative or “dry” form of age-related macular degeneration is a multifactorial progressive pathological process caused by hereditary predisposition, general and local disorders of lipid metabolism, negative changes in the blood supply to the eye, age-related destruction of the Bruch’s membrane and retinal pigment epithelium, the appearance of signs of local and systemic inflammation, the development of oxidative stress with the impact of toxic lipoperoxidation products on the structures of the posterior segment of the eye. Recent studies have discovered new ways of retinal pigment epithelial cell death in response to oxidative stress in AMD, in particular necroptosis, which, in addition to classical apoptosis, is considered the main mechanism of this process. It is noted that the development of AMD may be associated with an age-related decrease in the level of estrogen in women. The analysis of the data on the etiopathogenesis of age-related macular degeneration presented in the modern literature indicates the need for further research and generalization of local and general pathological processes developing in the dynamics of retinal visual function disorders by specialists of various scientific disciplines.
About the Authors
M. M. Bikbov
Ufa Eye Research Institute
Russian Federation
Russian Federation
Dr. Sc. (Med.), Professor, Corresponding Member of the Academy of Sciences of the Republic of Bashkortostan, Director,
Pushkina str. 90, Ufa 450008
T. A. Khalimov
Ufa Eye Research Institute
Russian Federation
Russian Federation
Ophthalmologist of the IV Microsurgical Department,
Pushkina str. 90, Ufa 450008
References
1. Bikbov MM, Fayzrakhmanov RR, Yarmukhametova AL. Age-related macular degeneration. Moscow: Aprel’; 2013. (In Russ.).
2. Egorov EA, Romanenko IA. Age-related macular degeneration. Questions of pathogenesis, diagnostics and treatment. Russian Journal of Clinical Ophthalmology. 2009; 10(1): 42-45. (In Russ.).
3. Wright CB, Ambati J. Dry age-related macular degeneration pharmacology. Handb Exp. Pharmacol. 2017; 242: 321-336. doi: 10.1007/164_2016_36
4. Heesterbeek TJ, Lores-Motta L, Hoyng CB, Lechanteur YT, den Hollander AI. Risk factors for progression of age-related macular degeneration. Ophthalmic Physiol. Opt. 2020; 40(2): 140-170. doi: 10.1111/opo.12675
5. Li J, Welchowski T, Schmid M, Mauschitz M, Holz F, Finger R. Prevalence and incidence of age-related macular degeneration in Europe: A systematic review and meta-analysis. Br J Ophthalmol. 2020; 104(8): 1077-1084. doi: 10.1136/bjophthalmol-2019-314422
6. Hyungtaek Rim T, Ryo K, Tham YC, Kang SW, Ruamviboonsuk P, Bikbov MM, et al. Prevalence and pattern of geographic atrophy in Asia: The Asian Eye Epidemiology Consortium. Ophthalmology. 2020; 127(10):1371-1381. doi: 10.1016/j.ophtha.2020.04.019
7. Smolyakova GP, Egorov VV, Kolenko OV, Danilova LP, Solovyova YuB. Dry form of age-related macular degeneration. Modern approaches to prevention and drug treatment. Zdravookhranenie Dal’nego Vostoka. 2019; 3: 56-60. (In Russ.).
8. Age-related macular degeneration. In: Moshetova LK, Nesterova AP, Egorova EA (eds). Ophthalmology. Clinical guidelines. Moscow: GEOTAR-Media; 2006: 164-188. (In Russ.).
9. Klein R, Davis MD, Magli YL, Segal P, Klein BE, Hubbard L. The Wisconsin age-related maculopathy grading system. Ophthalmology. 1991; 98(7): 1128-1134. doi: 10.1016/s0161-6420(91)32186-9
10. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001; 119(10): 1417-1436. doi: 10.1001/archopht.119.10.1417
11. Kiseleva TN, Lagutina YuM, Kravchuk EA. Modern aspects of pathogenesis, clinical picture and drug treatment of non-exudative forms of age-related macular degeneration. Russian Journal of Clinical Ophthalmology. 2006; 3: 99-102. (In Russ.).
12. Chen LJ. Genetic association of age-related macular degeneration and polypoidal choroidal vasculopathy. Asia Pac J Ophthalmol (Phila). 2020; 9(2): 104-109. doi: 10.1097/01.APO.0000656976.47696.7d
13. Seddon JM, Francis PJ, George S, Schultz DW, Rosner B, Klein ML. Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. JAMA. 2007; 297(16): 1793-1800. doi: 10.1001/jama.297.16.1793
14. Cascella R, Ragazzo M, Strafella C, Missiroli F, Borgiani P, Angelucci F, et al. Age-related macular degeneration: Insights into inflammatory genes. J Ophthalmol. 2014; 2014: 582842. doi: 10.1155/2014/582842
15. Housset B. Free radicals and respiratory pathology. CR Seances Soc Biol Fil. 1994; 188(4): 321-333.
16. Ding X, Patel M, Chan C. Molecular pathology of agerelated macular degeneration. Prog Retin Eye Res. 2009; 28(1): 1-18. doi: 10.1016/j.preteyeres.2008.10.001
17. Cao K, Sahebjada S, Richardson A, Baird P. Do age-related macular degeneration genes show association with keratoconus? Eye Vis (Lond). 2019; 6: 38. doi: 10.1186/s40662-019-0164-z
18. Vingerling JR, Dielemans I, Bots ML, Hofman A, Grobbee DE, de Jong PT. Age-related macular degeneration is associated with atherosclerosis. The Rotterdam Study. Am J Epidemiol. 1995; 142(4): 404-409. doi: 10.1093/oxfordjournals.aje.a117648
19. Machalinska A. Age-related macular degeneration as a local manifestation of atherosclerosis – a novel insight into pathogenesis. Klin Oczna. 2013; 115(1): 74-78.
20. Cheung CM, Wong TY. Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment. J Intern Med. 2014; 276(2): 140-153. doi: 10.1111/joim.12227
21. Spraul CW, Grossniklaus HE. Characteristics of drusen and Bruch’s membrane changes in postmortem eyes with age-related macular degeneration. Arch Ophthalmol. 1997; 115(2): 267-273. doi: 10.1001/archopht.1997.01100150269022
22. Kansky D. Clinical ophthalmology: A systematic approach. Moscow: Logosfera; 2006. (In Russ.).
23. Mirzabekova KA. Age-related macular degeneration: Prevention and treatment. A review. Ophthalmology in Russia. 2014; 11(2): 4-9. (In Russ.).
24. Gelfand BD, Ambati J. A revised hemodynamic theory of age-related macular degeneration. Trends Mol Med. 2016; 22(8): 656-670. doi: 10.1016/j.molmed.2016.06.009
25. Pennington KL, DeAngelis MM. Epidemiology of agerelated macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vis (Lond). 2016; 3: 34. doi: 10.1186/s40662-016-0063-5
26. Klein R, Myers CE, Buitendijk GH, Rochtchina E, Gao X, de Jong PT, et al. Lipids, lipid genes, and incident age-related macular degeneration: The three continent age-related macular degeneration consortium. Am J Ophthalmol. 2014; 158(3): 513-524. doi: 10.1016/j.ajo.2014.05.027
27. Klein R, Lee KE, Tsai MY, Cruickshanks KJ, Gangnon RE, Klein BEK. Oxidized low-density lipoprotein and the incidence of age-related macular degeneration. Ophthalmology. 2019; 126(5): 752-758. doi: 10.1016/j.ophtha.2018.12.026
28. Mozhaytsev BS, Taratukhina IK, Ovechkina OP. Relationship between the activity of some enzymes with the content of trace elements and lipids and macular degeneration. Vestnik Oftalmologii. 1978; 2: 31-34. (In Russ.).
29. Possek E. Ueber senile Maculaveränderung bei Arterioskleros. Zeitschrift für Augenheilkunde. 1905; 13: 771-779.
30. Friedman E. A hemodynamic model of the pathogenesis of age-related macular degeneration. Am J Ophthalmol. 1997; 124(5): 677-682. doi: 10.1016/s0002-9394(14)70906-7
31. Friedman E. The role of the atherosclerotic process in the pathogenesis of age-related macular degeneration. Am J Ophthalmol. 2000; 130(5): 658-663. doi: 10.1016/s0002-9394(00)00643-7
32. Friedman E. Update of the vascular model of AMD. Br J Ophthalmol. 2004; 88(2): 161-163. doi: 10.1136/bjo.2003.036277
33. Friedman E. The pathogenesis of age-related macular degeneration. Am J Ophthalmol. 2008; 146(3): 348-349. doi: 10.1016/j.ajo.2008.05.017
34. Shaimova TA. Morphometric and hemodynamic criteria in assessing the clinical course of combined involutional eye pathology: Dissertation of Cand. Sc. (Med.). Chelyabinsk, 2017. (In Russ.).
35. van Leeuwen R, Ikram MK, Vingerling JR, Witteman JC, Hofman A, de Jong PT. Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: The Rotterdam Study. Invest Ophthalmol Vis Sci. 2003; 44(9): 3771-3777. doi: 10.1167/iovs.03-0121
36. Dorofeev DA. Lutein-containing nutraceuticals with antioxidant action in primary open-angle glaucoma, combined with the “dry” form of age-related macular degeneration. Ophthalmology in Russia. 2018; 15(3): 339-347. (In Russ.). doi: 10.18008/1816-5095-2018-3-339-347
37. Tartakovskaya AI, Alexandrova LM, Stepanyants ER. Blood coagulation system and anticoagulant drugs in the complex treatment of chorioretinal dystrophies. Vestnik Oftalmologii. 1977; 1: 74. (In Russ.).
38. Sagripanti A, Romani A, Ferretti A, Ragone MC, Baicchi U, Carpi A, et al. Blood coagulation parameters in retinal arterial occlusion. Graefes Arch Clin Exp Ophthalmol. 1999; 237(6): 480-483. doi: 10.1007/s004170050265
39. Penfold PL. Inflammation and age-related macular degeneration. JAMA. 2004; 292(1): 43. doi: 10.1001/jama.292.1.43-a
40. Chen M, Xu H. Inflammation in age-related macular degeneration: Implications for therapy. In: M. Khatami (ed.). Inflammatory Disease: Immunopathology, Clinical and Pharmacological Bases. 2012: 129-150.
41. Ermakova NA. The role of inflammation in the development of age-related macular dystrophy. Vestnik Oftalmologii. 2018; 6: 116-122. (In Russ.). doi: 10.17116/oftalma2018134061116
42. McGwin G, Hall TA, Xie A, Owsley C. The relation between C reactive protein and age related macular degeneration in the Cardiovascular Health Study. Br J Ophthalmol. 2005; 89(9): 1166-1170. doi: 10.1136/bjo.2005.067397
43. Schaumberg DA, Christen WG, Buring JE, Glynn RJ, Rifai N, Ridker PM. High-sensitivity C-reactive protein, other markers of inflammation, and the incidence of macular degeneration in women. Arch Ophthalmol. 2007; 125(3): 300-305. doi: 10.1001/archopht.125.3.300
44. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N. Association between C-reactive protein and age-related macular degeneration. JAMA. 2004; 291(6): 704-710. doi: 10.1001/jama.291.6.704
45. Seddon JM, George S, Rosner B, Rifai N. Progression of age-related macular degeneration: Prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers. Arch Ophthalmol. 2005. 123(6): 774-782. doi: 10.1001/archopht.123.6.774
46. Cousins SW, Espinosa-Heidmann DG, Csaky KG. Monocyte activation in patients with age-related macular degeneration: A biomarker of risk for choroidal neovascularization? Arch Ophthalmol. 2004; 122(7): 1013-1018. doi: 10.1001/ archopht.122.7.1013
47. Slepova OS, Eremeeva EA, Ryabina MV, Sorozhkina ES. Cytokines in lacrimal fluid and blood serum: Early biomarkers of age-related macular degeneration. Medical Immunology (Russia). 2015; 17(3): 245-252. (In Russ.). doi: 10.15789/1563-0625-2015-3-245-252
48. Ma W, Silverman S, Zhao L, Villasmil R, Campos M, Amaral J, et al. Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization. eLife. 2019; 8: 42049. doi: 10.7554/eLife.42049
49. Sarks JP, Sarks SH, Killingsworth MC. Morphology of early choroidal neovascularisation in age-related macular degeneration: Correlation with activity. Eye (Lond). 1997; 11(Pt 4): 515-522. doi: 10.1038/eye.1997.137
50. Oh H, Takagi H, Takagi C, Suzuma K, Otani A, Ishida K, et al. The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes. Invest Ophthalmol Vis Sci. 1999; 40(9): 1891-1898.
51. Killingsworth MC, Sarks JP, Sarks SH. Macrophages related to Bruch’s membrane in age-related macular degeneration. Eye (Lond). 1990; 4(Pt 4): 613-621. doi: 10.1038/eye.1990.86 52. Khalimov TA. Features of angiogenesis in eye diseases. RUDN Journal of Medicine. 2021; 25(2): 106-113. (In Russ.). doi: 10.22363/2313-0245-2021-25-2-106-113
52. Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid Med Cell Longev. 2016; 2016: 3164734. doi: 10.1155/2016/3164734
53. Mitchell P, Liew G, Gopinath B, Wong T. Age-related macular degeneration. Lancet. 2018; 392(10153): 1147-1159. doi: 10.1016/S0140-6736(18)31550-2
54. Bikbov MM, Shevchuk NE, Khalimov AR. Influence of ultraviolet crosslinking on the level of cytokines in the lacrimal fluid in patients with keratectasias. Cytokines and Inflammation. 2015; 14(2): 54-57. (In Russ.).
55. Bikbov MM, Khalimov AR, Usubov EL. Ultraviolet corneal crosslinking. Annals of the Russian academy of medical sciences. 2016; 71(3): 224-232. (In Russ.). doi: 10.15690/vramn562
56. Egorov EA, Gvetadze AA. Carotinoids and macular pigments. What do we know? Literature review. Russian Journal of Clinical Ophthalmology. 2015; 15(1): 28-32. (In Russ.).
57. Mironova EM. The role of pigment epithelium and structures interacting with it in the pathogenesis of eye diseases: Abstract of Dissertation of Dr. Sc. (Biol.). Moscow, 1990. (In Russ.).
58. Liang X, Wang Z, Gao M, Wu S, Zhang J, Liu Q, et al. Cyclic stretch induced oxidative stress by mitochondrial and NADPH oxidase in retinal pigment epithelial cells. BMC Ophthalmol. 2019; 19(1): 79. doi: 10.1186/s12886-019-1087-0
59. Hanus J, Anderson C, Wang S. RPE necroptosis in response to oxidative stress and in AMD. Ageing Res Rev. 2015; 24(Pt B): 286- 298. doi: 10.1016/j.arr.2015.09.002
60. Yang M, So KF, Lam W, Lo A. Novel programmed cell death as therapeutic targets in age-related macular degeneration? Int J Mol Sci. 2020; 21(19): 7279. doi: 10.3390/ijms21197279
61. Suzuki M, Kamei M, Itabe H, Yoneda K, Bando H, Kume N, et al. Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration. Mol Vis. 2007; 13: 772-778.
62. Barinov EF. Molecular mechanisms of druze formation in the retina in age-related macular degeneration. Ophthalmology in Russia.2020; 17(3S): 550-555.(In Russ.).doi: 10.18008/1816-5095-2020-3S-550-555
63. Hutchinson C, Walker J, Davidson C. Oestrogen, ocular function and low-level vision: A review J Endocrinol. 2014; 223(2): R9-R18. doi: 10.1530/JOE-14-0349
64. Kaarniranta K, Machalinska A, Vereb Z, Salminen A, Petrovski G, Kauppinen A. Estrogen signalling in the pathogenesis of age-related macular degeneration. Curr Eye Res. 2015; 40(2): 226-233. doi: 10.3109/02713683.2014.925933
Review
For citations:
Bikbov M.M., Khalimov T.A. Etiopathogenesis of non-exudative age-related macular degeneration (literature review). Acta Biomedica Scientifica. 2022;7(1):96-105. (In Russ.) https://doi.org/10.29413/ABS.2022-7.1.12
Views:
939
Email this article 
