The modern view of the state of the problem of age-macular degeneration, its connection with genetics

Authors

  • Yosip Saldan National Pirogov Memorial Medical University, Vinnytsya, Ukraine

DOI:

https://doi.org/10.15587/2519-4798.2023.282363

Keywords:

age-related macular degeneration, Alzheimer's disease, genetics

Abstract

Age-related macular degeneration (AMD) is now recognized as a complex genetic condition in which any number of genes influence a person's susceptibility to developing the disorder. Earlier studies of genetics, in addition to population-based genetic epidemiologic approaches, strongly emphasized the importance of genetics in AMD. Although the degree of heritability and the number of genes are related, the behavioural and genetic variability of the disease remains unclear, but access to modern diagnostic methods, ophthalmological and molecular genetics, expands our understanding of the mechanisms of its development and progression. One of the main problems of ophthalmological research in the coming years will be to determine the genetic cause of AMD. The use of various genetic methods provides the best chance of determining the function of one or more genes in the pathophysiology of this condition.

The aim of this article is to conduct an analysis of the current literature to understand the pathogenesis of AMD at the molecular level and to provide the opportunity to establish and investigate new treatment methods, as well as to provide a treatment strategy that combines nutritional, environmental, and pharmacological methods to reduce the effect of genetic susceptibility and preserve vision.

Materials and methods - sources of information in the form of scientific articles, research works and monographs were selected for the analytical review of the literature. Databases such as PubMed, Google Scholar, Scopus and Web Of Science were used.

Research results - in the analytical review of modern domestic and foreign literature, it was determined that the use of various genetic methods provides the best chances to determine the function of one or more genes in the pathophysiology of age-related macular degeneration.

Conclusions - one of the main problems of ophthalmological research in the coming years will be to determine the genetic cause of AMD. The use of various genetic methods provides the best chance of determining the function of one or more genes in the pathophysiology of this condition. The goals are to identify people at high risk of developing AMD before they develop symptoms or serious pathology, to understand the pathogenesis of AMD at the molecular level and to enable the establishment and investigation of new treatments, as well as to provide a treatment strategy that combines nutritional, environmental, and pharmacological methods to reduce the effect of genetic susceptibility and preserve vision

Author Biography

Yosip Saldan, National Pirogov Memorial Medical University, Vinnytsya

Doctor of Medical Sciences, Professor

Department of Ophthalmology

References

  1. Querques, G., Merle, B. M. J., Pumariega, N. M., Benlian, P., Delcourt, C., Zourdani, A. et al. (2016). Dynamic Drusen Remodelling in Participants of the Nutritional AMD Treatment-2 (NAT-2) Randomized Trial. PLOS ONE, 11 (2), e0149219. doi: https://doi.org/10.1371/journal.pone.0149219
  2. Rein, D. B., Wittenborn, J. S., Zhang, X., Honeycutt, A. A., Lesesne, S. B., Saaddine, J. (2009). Vision Health Cost-Effectiveness Study Group. Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments. Archives of Ophthalmology, 127 (4), 533–540. doi: https://doi.org/10.1001/archophthalmol.2009.58
  3. Blasiak, J., Sobczuk, P., Pawlowska, E., Kaarniranta, K. (2022). Interplay between aging and other factors of the pathogenesis of age-related macular degeneration. Ageing Research Reviews, 81, 101735. doi: https://doi.org/10.1016/j.arr.2022.101735
  4. Shargorods`ka, І., Frolova, S. (2019). The effectiveness of determining risk factors for the development of age-related macular degeneration. Shevalovskі chitannya 19. Zaporіzhzhya, 56–59.
  5. Chew, E. Y., Clemons, T., SanGiovanni, J. P., Danis, R., Domalpally, A., McBee, W. Et al. (2012). The Age-related Eye Disease Study 2 (AREDS2). Ophthalmology, 119 (11), 2282–2289. doi: https://doi.org/10.1016/j.ophtha.2012.05.027
  6. Evans, J. B., Syed, B. A. (2013). New hope for dry AMD? Nature Reviews Drug Discovery, 12 (7), 501–502. doi: https://doi.org/10.1038/nrd4038
  7. Huang, D., Heath Jeffery, R. C., Aung-Htut, M. T., McLenachan, S., Fletcher, S., Wilton, S. D., Chen, F. K. (2021). Stargardt disease and progress in therapeutic strategies. Ophthalmic Genetics, 43 (1), 1–26. doi: https://doi.org/10.1080/13816810.2021.1966053
  8. Kubota, R., Birch, D. G., Gregory, J. K., Koester, J. M. (2020). Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease. British Journal of Ophthalmology, 106 (3), 403–408. doi: https://doi.org/10.1136/bjophthalmol-2020-317712
  9. Antonioli, L., Blandizzi, C., Pacher, P., Haskó, G. (2019). The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases. Pharmacological Reviews, 71 (3), 345–382. doi: https://doi.org/10.1124/pr.117.014878
  10. Augood, C. A. (2006). Prevalence of Age-Related Maculopathy in Older Europeans. Archives of Ophthalmology, 124 (4), 529. doi: https://doi.org/10.1001/archopht.124.4.529
  11. Burnstock, G. (2017). Purinergic Signaling in the Cardiovascular System. Circulation Research, 120 (1), 207–228. doi: https://doi.org/10.1161/circresaha.116.309726
  12. Kovalchuk, Kh. V. (2020). Geographic atrophy in patients with dry age-related macular degeneration: current problems of pathogenesis and prospects for progression diagnostics. Bulletin of Problems Biology and Medicine, 4 (2), 107–111. doi: https://doi.org/10.29254/2077-4214-2019-4-2-154-107-111
  13. Mogilevskyy, S. Yu., Kovalchuk, Kh. V. (2020). System analysis of factors in the pathogenesis of drusen formation in AMD. Oftalmologicheskii Zhurnal, 85 (2), 50–55. doi: https://doi.org/10.31288/oftalmolzh202025055
  14. van Lookeren Campagne, M., LeCouter, J., Yaspan, B. L., Ye, W. (2013). Mechanisms of age-related macular degeneration and therapeutic opportunities. The Journal of Pathology, 232 (2), 151–164. doi: https://doi.org/10.1002/path.4266
  15. Frolova, S., Shargorods`ka, І. (2018). The effectiveness of determining risk factors for the development of age-related macular degeneration. The second international scientific congress of scientists of Europe as part of II International Scientific Forum of Scientists «East – West». Vienna.
  16. Laíns, I., Kelly, R. S., Miller, J. B., Silva, R., Vavvas, D. G., Kim, I. K. et al. (2018). Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers. Ophthalmology, 125 (2), 245–254. doi: https://doi.org/10.1016/j.ophtha.2017.08.008
  17. Klaver, C. C. W., Kliffen, M., van Duijn, C. M., Hofman, A., Cruts, M., Grobbee, D. E. et al. (1998). Genetic Association of Apolipoprotein E with Age-Related Macular Degeneration. The American Journal of Human Genetics, 63 (1), 200–206. doi: https://doi.org/10.1086/301901
  18. Gehrs, K. M., Anderson, D. H., Johnson, L. V., Hageman, G. S. (2006). Age‐related macular degeneration – emerging pathogenetic and therapeutic concepts. Annals of Medicine, 38 (7), 450–471. doi: https://doi.org/10.1080/07853890600946724
  19. Gehrs, K. M., Jackson, J. R., Brown, E. N., Allikmets, R., Hageman, G. S. (2010). Complement, age-related macular degeneration and a vision of the future. Archives of ophthalmology, 128 (3), 349–358. doi: https://doi.org/10.1001/archophthalmol.2010.18
  20. Fletcher, E. L. (2017). 2016 Glenn A. Fry Award Lecture: Mechanisms and Potential Treatments of Early Age-Related Macular Degeneration. Optometry and Vision Science, 94 (10), 939–945. doi: https://doi.org/10.1097/opx.0000000000001124
  21. Kylhammar, D., Bune, L. T., Rådegran, G. (2014). P2Y1 and P2Y12 receptors in hypoxia- and adenosine diphosphate-induced pulmonary vasoconstriction in vivo in the pig. European Journal of Applied Physiology, 114 (9), 1995–2006. doi: https://doi.org/10.1007/s00421-014-2921-y
  22. Chew, E. Y., Klein, M. L., Clemons, T. E., Agrón, E., Ratnapriya, R., Edwards, A. O. et al. (2014). No Clinically Significant Association between CFH and ARMS2 Genotypes and Response to Nutritional Supplements. Ophthalmology, 121 (11), 2173–2180. doi: https://doi.org/10.1016/j.ophtha.2014.05.008
  23. Adams, M. K. M., Simpson, J. A., Richardson, A. J., English, D. R., Aung, K. Z., Makeyeva, G. A. et al. (2012). Apolipoprotein E Gene Associations in Age-related Macular Degeneration: The Melbourne Collaborative Cohort Study. American Journal of Epidemiology, 175 (6), 511–518. doi: https://doi.org/10.1093/aje/kwr329
  24. Hu, M. L., Quinn, J., Xue, K. (2021). Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration. Life, 11 (7), 635. doi: https://doi.org/10.3390/life11070635
  25. Dunaief, J. L. (2002). The Role of Apoptosis in Age-Related Macular Degeneration. Archives of Ophthalmology, 120 (11), 1435. doi: https://doi.org/10.1001/archopht.120.11.1435
  26. Hu, M. L., Quinn, J., Xue, K. (2021). Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration. Life, 11 (7), 635. doi: https://doi.org/10.3390/life11070635
  27. Phillips, M. C. (2014). Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life, 66 (9), 616–623. doi: https://doi.org/10.1002/iub.1314
  28. Ventura, A. L. M., dos Santos-Rodrigues, A., Mitchell, C. H., Faillace, M. P. (2019). Purinergic signaling in the retina: From development to disease. Brain Research Bulletin, 151, 92–108. doi: https://doi.org/10.1016/j.brainresbull.2018.10.016
  29. Liu, C.-C., Kanekiyo, T., Xu, H., Bu, G. (2013). Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nature Reviews Neurology, 9 (2), 106–118. doi: https://doi.org/10.1038/nrneurol.2012.263
  30. Elias-Sonnenschein, L. S., Viechtbauer, W., Ramakers, I. H. G. B., Verhey, F. R. J., Visser, P. J. (2011). Predictive value of APOE- 4 allele for progression from MCI to AD-type dementia: a meta-analysis. Journal of Neurology, Neurosurgery & Psychiatry, 82 (10), 1149–1156. doi: https://doi.org/10.1136/jnnp.2010.231555
  31. Vessey, K. A., Gu, B. J., Jobling, A. I., Phipps, J. A., Greferath, U., Tran, M. X. et al. (2017). Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice. The American Journal of Pathology, 187 (8), 1670–1685. doi: https://doi.org/10.1016/j.ajpath.2017.04.016
  32. Klein, R., Klein, B. E. K., Linton, K. L. P. (1992). Prevalence of Age-related Maculopathy. Ophthalmology, 99 (6), 933–943. doi: https://doi.org/10.1016/s0161-6420(92)31871-8
  33. Huang, Z., Xie, N., Illes, P., Di Virgilio, F., Ulrich, H., Semyanov, A. et al. (2021). From purines to purinergic signalling: molecular functions and human diseases. Signal Transduction and Targeted Therapy, 6 (1). doi: https://doi.org/10.1038/s41392-021-00553-z
  34. Velilla, S., García-Medina, J. J., García-Layana, A., Dolz-Marco, R., Pons-Vázquez, S., Pinazo-Durán, M. D. et al. (2013). Smoking and Age-Related Macular Degeneration: Review and Update. Journal of Ophthalmology, 2013, 1–11. doi: https://doi.org/10.1155/2013/895147
  35. Willeford, K. T., Rapp, J. (2012). Smoking and Age-Related Macular Degeneration. Optometry and Vision Science, 89 (11), 1662–1666. doi: https://doi.org/10.1097/opx.0b013e31826c5df2
  36. Davis, M. D., Gangnon, R. E., Lee, L. Y., Hubbard, L. D., Klein, B. E., Klein, R. et al. (2005). Age-Related Eye Disease Study Group. The Age-Related Eye Disease Study severity scale for age-related macular degeneration. Archives of Ophthalmology, 123 (11), 1484–1498. doi: https://doi.org/10.1001/archopht.123.11.1484
  37. Qiu, F., Meng, T., Chen, Q., Zhou, K., Shao, Y., Matlock, G. et al. (2019). Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Experimental Diabetic Retinopathy and Neovascular Age-Related Macular Degeneration. Molecular Pharmaceutics, 16 (5), 1958–1970. doi: https://doi.org/10.1021/acs.molpharmaceut.8b01319
  38. Ebrahimi, K. B., Fijalkowski, N., Cano, M., Handa, J. T. (2013). Decreased membrane complement regulators in the retinal pigmented epithelium contributes to age-related macular degeneration. The Journal of Pathology, 229 (5), 729–742. doi: https://doi.org/10.1002/path.4128
  39. Wong, W. L., Su, X., Li, X., Cheung, C. M. G., Klein, R., Cheng, C.-Y., Wong, T. Y. (2014). Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global Health, 2 (2), e106–e116. doi: https://doi.org/10.1016/s2214-109x(13)70145-1

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Published

2023-03-31

How to Cite

Saldan, Y. (2023). The modern view of the state of the problem of age-macular degeneration, its connection with genetics. ScienceRise: Medical Science, (2(53), 38–42. https://doi.org/10.15587/2519-4798.2023.282363

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Medical Science