Skip to main content
Log in

Current Data on the Age-Related Macular Degeneration Pathophysiology: Focus on Growth Factors and Neurotrophins

  • REVIEWS
  • Published:
Advances in Gerontology Aims and scope Submit manuscript

Abstract

Age is a main risk factor for age-related macular degeneration (AMD), a complex multifactorial neurodegenerative retinal disease that is becoming the leading cause of vision loss in people over 55 years in developed countries. The risk of developing and rate of progression of AMD, as well as response to therapy, depend on the interaction of multiple genetic and environmental factors. In advanced stage, AMD is classified into dry atrophic (dry) or neovascular (wet) form. Intravitreal injection of anti-vascular endothelial growth factor agents is currently the first-line therapy for neovascular AMD. Unfortunately, therapy for dry AMD is still challenging, owing to an insufficient knowledge of the exact pathogenetic mechanisms. Considering the heterogeneity of AMD and the complexity of influencing age-dependent physiological processes, aging and immune disorders, the most realistic seems to be the further development of antiangiogenic therapy with an expansion of the range of targets, prolongation of their action and improvement of the delivery system. The neuroprotective potential of exogenous neurotrophins for retinal neurons has been proven; however, in order to develop effective drugs for the dry form of AMD based on them, it is necessary to resolve the issue of ways to effectively deliver them to the retina. In this review we discuss the current data on the AMD pathophysiology with focus on the role of vascular growth factors and neurotrophins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

REFERENCES

  1. Guymer, R.H. and Campbell, T.G., Age-related macular degeneration, Lancet, 2023, vol. 401, no. 10386, pp. 1459–1472. https://doi.org/10.1016/S0140-6736(22)02609-5

    Article  CAS  PubMed  Google Scholar 

  2. Bhutto, I. and Lutty, G., Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex, Mol. Aspects Med., 2012, vol. 33, no. 4, pp. 295–317. https://doi.org/10.1016/j.mam.2012.04.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zaytseva, O.V., Neroeva, N.V., Okhotsimskaya, T.D., and Bobykin, E.V., Anti-VEGF therapy for neovascular age-related macular degeneration: Causes of incomplete response, Vestn. Oftalmol., 2021, vol. 137, no. 5, pp. 152–159. https://doi.org/10.17116/oftalma2021137051152

    Article  CAS  PubMed  Google Scholar 

  4. Kauppinen, A., Paterno, J.J., Blasiak, J., Salminen, A., and Kaarniranta, K., Inflammation and its role in age-related macular degeneration, Cell Mol. Life Sci., 2016, vol. 73, no. 9, pp. 1765–1786. https://doi.org/10.1007/s00018-016-2147-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rozing, M.P., Durhuus, J.A., Krogh Nielsen, M., Subhi, Y., Kirkwood, T.B., Westendorp, R.G., and Sorensen, T.L., Age-related macular degeneration: A two-level model hypothesis, Prog. Retin. Eye Res., 2020, vol. 76, p. 100825. https://doi.org/10.1016/j.preteyeres.2019.100825

    Article  PubMed  Google Scholar 

  6. Wakatsuki, Y., Shinojima, A., Kawamura, A., and Yuzawa, M., Correlation of aging and segmental choroidal thickness measurement using swept source optical coherence tomography in healthy eyes, PLoS One, 2015, vol. 10, no. 12, p. e0144156. https://doi.org/10.1371/journal.pone.0144156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lee, K.S., Lin, S., Copland, D.A., Dick, A.D., and Liu, J., Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration, J. Neuroinflammation, 2018, vol. 18, no. 1, p. 32. https://doi.org/10.1186/s12974-021-02088-0

    Article  CAS  Google Scholar 

  8. Mitre, M., Mariga, A., and Chao, M.V., Neurotrophin signalling: Novel insights into mechanisms and pathophysiology, Clin. Sci. (Lond.), 2017, vol. 131, no. 1, pp. 13–23. https://doi.org/10.1042/CS20160044

    Article  CAS  PubMed  Google Scholar 

  9. Boyer, N.P., Higbee, D., Currin, M.B., Blakeley, L.R., Chen, C., Ablonczy, Z., Crouch, R.K., and Koutalos, Y., Lipofuscin and N-retinylidene-N-retinylethanolamine (A2E) accumulate in retinal pigment epithelium in absence of light exposure: Their origin is 11-cis-retinal, J. Biol. Chem., 2012, vol. 287, no. 26, pp. 22 276–22 286. https://doi.org/10.1074/jbc.M111.329235

    Article  CAS  Google Scholar 

  10. Liu, J., Itagaki, Y., Ben-Shabat, S., Nakanishi, K., and Sparrow, J.R., The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2-PE, in the photoreceptor outer segment membrane, J. Biol. Chem., 2000, vol. 275, no. 38, pp. 29 354–29 360. https://doi.org/10.1074/jbc.M910191199

    Article  Google Scholar 

  11. Macchioni, L., Chiasserini, D., Mezzasoma, L., Davidescu, M., Orvietani, P.L., Fettucciari, K., Salviati, L., Cellini, B., and Bellezza, I., Crosstalk between long-term sublethal oxidative stress and detrimental inflammation as potential drivers for age-related retinal degeneration, Antioxidants, 2020, vol. 10, no. 1, p. 25, https://doi.org/10.3390/antiox10010025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kaarniranta, K., Uusitalo, H., Blasiak, J., Felszeghy, S., Kannan, R., Kauppinen, A., Salminen, A., Sinha, D., and Ferrington, D., Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration, Prog. Retin. Eye Res., 2020, vol. 79, p. 100858. https://doi.org/10.1016/j.preteyeres.2020.100858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kim, J., Lee, Y.J., and Won, J.Y., Molecular mechanisms of retinal pigment epithelium dysfunction in age-related macular degeneration, Int. J. Mol. Sci., 2021, vol. 22, no. 22, p. 12 298. https://doi.org/10.3390/ijms222212298

    Article  CAS  Google Scholar 

  14. Minasyan, L., Sreekumar, P.G., Hinton, D.R., and Kannan, R., Protective mechanisms of the mitochondrial-derived peptide humanin in oxidative and endoplasmic reticulum stress in RPE cells, Oxid. Med. Cell. Longev., 2017, p. 1675230. https://doi.org/10.1155/2017/1675230

  15. Blasiak, J., Pawlowska, E., Szczepanska, J., and Kaarniranta, K., Interplay between autophagy and the ubiquitin–proteasome system and its role in the pathogenesis of age-related macular degeneration, Int. J. Mol. Sci., 2019, vol. 20, no. 1, p. 210. https://doi.org/10.3390/ijms20010210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Telegina, D.V., Kozhevnikova, O.S., and Kolosova, N.G., Molecular mechanisms of cell death in retina during development of age-related macular degeneration, Adv. Gerontol., 2017, vol. 7, pp. 17–24. https://doi.org/10.1134/S2079057017010155

    Article  Google Scholar 

  17. Kaarniranta, K., Tokarz, P., Koskela, A., Paterno, J., and Blasiak, J., Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration, Cell Biol. Toxicol., 2017, vol. 33, no. 2, pp. 113–128. https://doi.org/10.1007/s10565-016-9371-8

    Article  CAS  PubMed  Google Scholar 

  18. Hanus, J., Anderson, C., and Wang, S., RPE necroptosis in response to oxidative stress and in AMD, Ageing Res. Rev., 2015, vol. 24, no. Pt-B, pp. 286–298. https://doi.org/10.1016/j.arr.2015.09.002

  19. Chen, M., Glenn, J.V., Dasari, S., McVicar, C., Ward, M., Colhoun, L., Quinn, M., Bierhaus, A., Xu, H., and Stitt, A.W., RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization, PLoS One, 2014, vol. 9, no. 2, p. e89548. https://doi.org/10.1371/journal.pone.0089548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Geerlings, M.J., de Jong, E.K., and den Hollander, A.I., The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment, Mol. Immunol., 2017, vol. 84, pp. 65–76. https://doi.org/10.1016/j.molimm.2016.11.016

  21. Mullins, R.F., Schoo, D.P., Sohn, E.H., Flamme-Wiese, M.J., Workamelahu, G., Johnston, R.M., Wang, K., Tucker, B.A., and Stone, E.M., The membrane attack complex in aging human choriocapillaris: Relationship to macular degeneration and choroidal thinning, Am. J. Pathol., 2014, vol. 184, no. 11, pp. 3142–3153. https://doi.org/10.1016/j.ajpath.2014.07.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lynch, A.M., Mandava, N., Patnaik, J.L., Frazer-Abel, A.A., Wagner, B.D., Palestine, A.G., Mathias, M.T., Siringo, F.S., Cathcart, J.N., and Holers, V.M., Systemic activation of the complement system in patients with advanced age-related macular degeneration, Eur. J. Ophthalmol., 2020, vol. 30, no. 5, pp. 1061–1068. https://doi.org/10.1177/1120672119857896

    Article  PubMed  Google Scholar 

  23. Kozhevnikova, O.S., Fursova, A.Z., Derbeneva, A.S., Nikulich, I.F., Tarasov, M.S., Devyatkin, V.A., Rumyantseva, Y.V., Telegina, D.V., and Kolosova, N.G., Association between polymorphisms in CFH, ARMS2, CFI, and C3 genes and response to anti-VEGF treatment in neovascular age-related macular degeneration, Biomedicines, 2022, vol. 10, no. 7, p. 1658. https://doi.org/10.3390/biomedicines10071658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cao, S., Ko, A., Partanen, M., Pakzad-Vaezi, K., Merkur, A.B., Albiani, D.A., Kirker, A.W., Wang, A., Cui, J.Z., Forooghian, F., and Matsubara, J.A., Relationship between systemic cytokines and complement factor H Y402H polymorphism in patients with dry age-related macular degeneration, Am. J. Ophthalmol., 2013, vol. 156, no. 6, pp. 1176–1183. https://doi.org/10.1016/j.ajo.2013.08.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Espinosa-Heidmann, D.G., Suner, I.J., Hernandez, E.P., Monroy, D., Csaky, K.G., and Cousins, S.W., Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization, Invest. Ophthalmol. Vis. Sci., 2003, vol. 44, no. 8, pp. 3586–3592. https://doi.org/10.1167/iovs.03-0038

    Article  PubMed  Google Scholar 

  26. Zhou, J., He, S., Zhang, N., Spee, C., Zhou, P., Ryan, S.J., Kannan, R., and Hinton, D.R., Neutrophils compromise retinal pigment epithelial barrier integrity, J. Biomed. Biotechnol., 2010, vol. 2010, p. 289360. https://doi.org/10.1155/2010/289360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhao, Z., Liang, Y., Liu, Y., Xu, P., Flamme-Wiese, M.J., Sun, D., Sun, J., Mullins, R.F., Chen, Y., and Cai, J., Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury, FASEB J., 2017, vol. 31, no. 11, pp. 4903–4916. https://doi.org/10.1096/fj.201700533R

  28. Ferrara, N., Mass, R.D., Campa, C., and Kim, R., Targeting VEGF-A to treat cancer and age-related macular degeneration, Annu. Rev. Med., 2007, vol. 58, pp. 491–504. https://doi.org/10.1146/annurev.med.58.061705.145635

    Article  CAS  PubMed  Google Scholar 

  29. de Oliveira Dias, J.R., Rodrigues, E.B., Maia, M., Magalhaes, O., Jr., Penha, F.M., and Farah, M.E., Cytokines in neovascular age-related macular degeneration: Fundamentals of targeted combination therapy, Br. J. Ophthalmol., 2011, vol. 95, no. 12, pp. 1631–1637. https://doi.org/10.1136/bjo.2010.186361

    Article  PubMed  Google Scholar 

  30. Ciulla, T.A. and Rosenfeld, P.J., Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration, Curr. Opin. Ophthalmol., 2009, vol. 20, no. 3, pp. 158–165. https://doi.org/10.1097/ICU.0b013e32832d25b3

    Article  PubMed  Google Scholar 

  31. Apte, R.S., Chen, D.S., and Ferrara, N., VEGF in signaling and disease: Beyond discovery and development, Cell, 2019, vol. 176, no. 6, pp. 1248–1264. https://doi.org/10.1016/j.cell.2019.01.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cao, Y., Positive and negative modulation of angiogenesis by VEGFR1 ligands, Sci. Signal., 2009, vol. 2, no. 59, p. re1. https://doi.org/10.1126/scisignal.259re1

    Article  PubMed  Google Scholar 

  33. Klettner, A., Kaya, L., Flach, J., Lassen, J., Treumer, F., and Roider, J., Basal and apical regulation of VEGF-A and placenta growth factor in the RPE/choroid and primary RPE, Mol. Vis., 2015, vol. 21, pp. 736–748.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Arjunan, P., Lin, X., Tang, Z., et al., VEGF-B is a potent antioxidant, Proc. Natl. Acad. Sci. U. S. A., 2018, vol. 115, no. 41, pp. 10351–10356. https://doi.org/10.1073/pnas.1801379115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Li, X., Kumar, A., Zhang, F., Lee, C., and Tang, Z., Complicated life, complicated VEGF-B, Trends Mol. Med., 2012, vol. 18, no. 2, pp. 119–127. https://doi.org/10.1016/j.molmed.2011.11.006

    Article  CAS  PubMed  Google Scholar 

  36. Zhong, X., Huang, H., Shen, J., Zacchigna, S., Zentilin, L., Giacca, M., and Vinores, S.A., Vascular endothelial growth factor-B gene transfer exacerbates retinal and choroidal neovascularization and vasopermeability without promoting inflammation, Mol Vis., 2011, vol. 17, pp. 492–507.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang, F., Tang, Z., Hou, X., et al., VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis, Proc. Natl. Acad. Sci. U. S. A., 2009, vol. 106, no. 15, pp. 6152–6157. https://doi.org/10.1073/pnas.0813061106

    Article  PubMed  PubMed Central  Google Scholar 

  38. Uemura, A., Fruttiger, M., D’Amore, P.A., De Falco, S., Joussen, A.M., Sennlaub, F., Brunck, L.R., Johnson, K.T., Lambrou, G.N., Rittenhouse, K.D., and Langmann, T., VEGFR1 signaling in retinal angiogenesis and microinflammation, Prog. Retin. Eye Res., 2021, vol. 84, 100954. https://doi.org/10.1016/j.preteyeres.2021.100954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Dugel, P.U., Boyer, D.S., Antoszyk, A.N., Steinle, N.C., Varenhorst, M.P., Pearlman, J.A., Gillies, M.C., Finger, R.P., Baldwin, M.E., and Leitch, I.M., Phase 1 study of OPT-302 inhibition of vascular endothelial growth factors C and D for neovascular age-related macular degeneration, Ophthalmol. Retina, 2020, vol. 4, no. 3, pp. 250–263. https://doi.org/10.1016/j.oret.2019.10.008

    Article  PubMed  Google Scholar 

  40. Cunningham, F., Van Bergen, T., Canning, P., Lengyel, I., Feyen, J.H.M., and Stitt, A.W., The placental growth factor pathway and its potential role in macular degenerative disease, Curr Eye Res., 2019, vol. 44, no. 8, pp. 813–822. https://doi.org/10.1080/02713683.2019.1614197

    Article  PubMed  Google Scholar 

  41. Dewerchin, M. and Carmeliet, P., PlGF: A multitasking cytokine with disease-restricted activity, Cold Spring Harb. Perspect. Med., 2012, vol. 2, no. 8, p. a011056.https://doi.org/10.1101/cshperspect.a011056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. De Falco, S., The discovery of placenta growth factor and its biological activity, Exp. Mol. Med., 2012, vol. 44, no. 1, pp. 1–9. https://doi.org/10.3858/emm.2012.44.1.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Patel, P. and Sheth, V., New and innovative treatments for neovascular age-related macular degeneration (nAMD), J. Clin. Med., 2021, vol. 10, no. 11, p. 2436. https://doi.org/10.3390/jcm10112436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Camby, I., Le Mercier, M., Lefranc, F., and Kiss, R., Galectin-1: A small protein with major functions, Glycobiology, 2006, vol. 16, no. 11, pp. 137R–157R. https://doi.org/10.1093/glycob/cwl025

    Article  CAS  PubMed  Google Scholar 

  45. Kanda, A., Noda, K., Saito, W., and Ishida, S., Aflibercept traps galectin-1, an angiogenic factor associated with diabetic retinopathy, Sci. Rep., 2015, vol. 5, p. 17946. https://doi.org/10.1038/srep17946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hollborn, M., Tenckhoff, S., Seifert, M., Kohler, S., Wiedemann, P., Bringmann, A., and Kohen, L., Human retinal epithelium produces and responds to placenta growth factor, Graefes Arch. Clin. Exp. Ophthalmol., 2006, vol. 244, no. 6, pp. 732–741. https://doi.org/10.1007/s00417-005-0154-9

    Article  CAS  PubMed  Google Scholar 

  47. Rakic, J.M., Lambert, V., Devy, L., Luttun, A., Carmeliet, P., Claes, C., Nguyen, L., Foidart, J.M., Noel, A., and Munaut, C., Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization, Invest. Ophthalmol. Vis. Sci., 2003, vol. 44, no. 7, pp. 3186–3193. https://doi.org/10.1167/iovs.02-1092

    Article  PubMed  Google Scholar 

  48. Motohashi, R., Noma, H., Yasuda, K., Kotake, O., Goto, H., and Shimura, M., Dynamics of inflammatory factors in aqueous humor during ranibizumab or aflibercept treatment for age-related macular degeneration, Ophthalmic. Res., 2017, vol. 58, no. 4, pp. 209–216. https://doi.org/10.1159/000478705

    Article  CAS  PubMed  Google Scholar 

  49. Pongsachareonnont, P., Mak, M.Y.K., Hurst, C.P., and Lam, W.C., Neovascular age-related macular degeneration: Intraocular inflammatory cytokines in the poor responder to ranibizumab treatment, Clin. Ophthalmol., 2018, vol. 12, pp. 1877–1885. https://doi.org/10.2147/OPTH.S171636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Heier, J.S., Singh, R.P., Wykoff, C.C., Csaky, K.G., Lai, T.Y.Y., Loewenstein, A., Schlottmann, P.G., Paris, L.P., Westenskow, P.D., and Quezada-Ruiz, C., The Angiopoietin/Tie pathway in retinal vascular diseases: A review, Retina, 2021, vol. 41, no. 1, pp. 1–19. https://doi.org/10.1097/IAE.0000000000003003

    Article  CAS  PubMed  Google Scholar 

  51. Lee, J., Park, D.Y., Park, D.Y., Park, I., Chang, W., Nakaoka, Y., Komuro, I., Yoo, O.J., and Koh, G.Y., Angiopoietin-1 suppresses choroidal neovascularization and vascular leakage, Invest. Ophthalmol. Vis. Sci., 2014, vol. 55, no. 4, pp. 2191–2199. https://doi.org/10.1167/iovs.14-13897

    Article  CAS  PubMed  Google Scholar 

  52. Hussain, R.M., Neiweem, A.E., Kansara, V., Harris, A., and Ciulla, T.A., Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease, Expert Opin. Investig. Drugs, 2019, vol. 28, no. 10, pp. 861–869. https://doi.org/10.1080/13543784.2019.1667333

    Article  CAS  PubMed  Google Scholar 

  53. Desideri, L.F., Traverso, C.E., and Nicolò, M., The emerging role of the Angiopoietin-Tie pathway as therapeutic target for treating retinal diseases, Expert Opin. Ther. Targets, 2022, vol. 26, no. 2, pp. 145–154. https://doi.org/10.1080/14728222.2022.2036121

    Article  CAS  Google Scholar 

  54. Frye, M., Dierkes, M., Küppers, V., Vockel, M., Tomm, J., Zeuschner, D., Rossaint, J., Zarbock, A., Koh, G.Y., Peters, K., Nottebaum, A.F., and Vestweber, D., Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin, J. Exp. Med., 2015, vol. 212, no. 13, pp. 2267–2287. https://doi.org/10.1084/jem.20150718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Campochiaro, P.A. and Peters, K.G., Targeting Tie2 for treatment of diabetic retinopathy and diabetic macular edema, Curr. Diab. Rep., 2016, vol. 16, no. 12, p. 126. https://doi.org/10.1007/s11892-016-0816-5

    Article  CAS  PubMed  Google Scholar 

  56. Wubben, T.J., Zacks, D.N., and Besirli, C.G., Retinal neuroprotection: Current strategies and future directions, Curr. Opin. Ophthalmol., 2019, vol. 30, no. 3, pp. 199–205. https://doi.org/10.1097/ICU.0000000000000558

    Article  PubMed  Google Scholar 

  57. Garcia, T.B., Hollborn, M., and Bringmann, A., Expression and signaling of NGF in the healthy and injured retina, Cytokine Growth Factor Rev., 2017, vol. 34, pp. 43–57. https://doi.org/10.1016/j.cytogfr.2016.11.005

    Article  CAS  PubMed  Google Scholar 

  58. Balzamino, B.O., Esposito, G., Marino, R., Keller, F., and Micera, A., NGF expression in reelin-deprived retinal cells: A potential neuroprotective effect, Neuromolecular Med., 2015, vol. 17, no. 3, pp. 314–325.https://doi.org/10.1007/s12017-015-8360-z35

  59. Taylor, S., Srinivasan, B., Wordinger, R.J., and Roque, R.S., Glutamate stimulates neurotrophin expression in cultured Muller cells, Brain Res. Mol. Brain Res., 2003, vol. 111, nos. 1–2, pp. 189–197. https://doi.org/10.1016/S0169-328X(03)00030-5

  60. Jansen, P., Giehl, K., Nyengaard, J.R., Teng, K., Lioubinski, O., Sjoegaard, S.S., Breiderhoff, T., Gotthardt, M., Lin, F., Eilers, A., Petersen, C.M., Lewin, G.R., Hempstead, B.L., Willnow, T.E., and Nykjaer, A., Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury, Nat. Neurosci., 2007, vol. 10, no. 11, pp. 1449–1457. https://doi.org/10.1038/nn2000

    Article  CAS  PubMed  Google Scholar 

  61. Harada, T., Harada, C., Kohsaka, S., Wada, E., Yoshida, K., Ohno, S., Mamada, H., Tanaka, K., Parada, L.F., and Wada, K., Microglia–Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration, J. Neurosci., 2002, vol. 22, no. 21, pp. 9228–9236. https://doi.org/10.1523/JNEUROSCI.22-21-09228.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Srinivasan, B., Roque, C.H., Hempstead, B.L., Al-Ubaidi, M.R., and Roque, R.S., Microglia-derived pronerve growth factor promotes photoreceptor cell death via p75 neurotrophin receptor, J. Biol. Chem., 2004, vol. 279, no. 40, pp. 41 839–41 845. https://doi.org/10.1074/jbc.M402872200

    Article  CAS  Google Scholar 

  63. Vogler, S., Hollborn, M., Berk, B.A., Pannicke, T., Seeger, J., Wiedemann, P., Reichenbach, A., and Bringmann, A., Ischemic regulation of brain-derived neurotrophic factor-mediated cell volume and TrkB expression in glial (Müller) and bipolar cells of the rat retina, Graefes Arch. Clin. Exp. Ophthalmol., 2016, vol. 254, no. 3, pp. 497–503. https://doi.org/10.1007/s00417-015-3250-5

    Article  CAS  PubMed  Google Scholar 

  64. Grishanin, R.N., Yang, H., Liu, X., Donohue-Rolfe, K., Nune, G.C., Zang, K., Xu, B., Duncan, J.L., Lavail, M.M., Copenhagen, D.R., and Reichardt, L.F., Retinal TrkB receptors regulate neural development in the inner, but not outer, retina, Mol. Cell Neurosci., 2008, vol. 38, no. 3, pp. 431–443. https://doi.org/10.1016/j.mcn.2008.04.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Espinet, C., Gonzalo, H., Fleitas, C., Menal, M.J., and Egea, J., Oxidative stress and neurodegenerative diseases: A neurotrophic approach, Curr. Drug Targets, 2015, vol. 16, no. 1, pp. 20–30. https://doi.org/10.2174/1389450116666150107153233

    Article  CAS  PubMed  Google Scholar 

  66. Kimura, A., Namekata, K., Guo, X., Harada, C., and Harada, T., Neuroprotection, growth factors and BDNF-TRKB signalling in retinal degeneration, Int. J. Mol. Sci., 2016, vol. 17, no. 9, p. 1584. https://doi.org/10.3390/ijms17091584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Tekin, I.M., Sekeroglu, M.A., Demirtas, C., Tekin, K., Doguizi, S., Bayraktar, S., and Yilmazbas, P., Brain-derived neurotrophic factor in patients with age-related macular degeneration and its correlation with retinal layer thicknesses, Invest. Ophthalmol. Vis. Sci., 2018, vol. 59, no. 7, pp. 2833–2840. https://doi.org/10.1167/iovs.18-24030

    Article  CAS  PubMed  Google Scholar 

  68. Tirassa, P., Rosso, P., and Iannitelli, A., Ocular nerve growth factor (NGF) and NGF eye drop application as paradigms to investigate ngf neuroprotective and reparative actions, Methods Mol. Biol., 2018, vol. 1727, pp. 19–38. https://doi.org/10.1007/978-1-4939-7571-6_2

    Article  CAS  PubMed  Google Scholar 

  69. Mitra, S., Behbahani, H., and Eriksdotter, M., Innovative therapy for Alzheimer’s Disease—with focus on biodelivery of NGF, Front. Neurosci., 2019, vol. 13, p. 38. https://doi.org/10.3389/fnins.2019.00038

    Article  PubMed  PubMed Central  Google Scholar 

  70. Abed, E., Corbo, G., and Falsini, B., Neurotrophin family members as neuroprotectants in retinal degenerations, BioDrugs, 2015, vol. 29, no. 1, pp. 1–13. https://doi.org/10.1007/s40259-014-0110-5

    Article  CAS  PubMed  Google Scholar 

  71. Rocco, M.L. and Balzamino, B.O., Petrocchi Passeri, P., Micera, A., and Aloe, L., Effect of purified murine NGF on isolated photoreceptors of a rodent developing retinitis pigmentosa, PLoS One, 2015, vol. 10, no. 4, p. e0124810. https://doi.org/10.1371/journal.pone.0124810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Falsini, B., Iarossi, G., Chiaretti, A., Ruggiero, A., Manni, L., Galli-Resta, L., Corbo, G., and Abed, E., NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study, J. Transl. Med., 2016, vol. 14, p. 8. https://doi.org/10.1186/s12967-015-0750-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Daly, C., Ward, R., Reynolds, A.L., Galvin, O., Collery, R.F., and Kennedy, B.N., Brain-derived neurotrophic factor as a treatment option for retinal degeneration, Adv. Exp. Med. Biol., 2018, vol. 1074, pp. 465–471. https://doi.org/10.1007/978-3-319-75402-4_57

    Article  CAS  PubMed  Google Scholar 

  74. Weber, A.J. and Harman, C.D., BDNF treatment and extended recovery from optic nerve trauma in the cat, Investig. Ophthalmol. Vis. Sci., 2013, vol. 54, no. 10, pp. 6594–6604. https://doi.org/10.1167/iovs.13-12683

    Article  CAS  Google Scholar 

  75. Feng, L., Puyang, Z., Chen, H., Liang, P., Troy, J.B., and Liu, X., Overexpression of brain-derived neurotrophic factor protects large retinal ganglion cells after optic nerve crush in mice, eNeuro, 2017, vol. 4, no. 1, p. ENEURO.0331-16.2016. https://doi.org/10.1523/ENEURO.0331-16.2016

  76. Afarid, M., Torabi-Nami, M., and Zare, B., Neuroprotective and restorative effects of the brain-derived neurotrophic factor in retinal diseases, J. Neurol. Sci., 2016, vol. 363, pp. 43–50. https://doi.org/10.1016/j.jns.2016.02.024

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research has been funded by the Russian Science Foundation (grant no. 21-15-00047) and by the State Budget Project FWNR-2022-0016.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. S. Kozhevnikova.

Ethics declarations

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This work does not contain any studies involving human and animal subjects.

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fursova, A.Z., Derbeneva, A.S., Vasilyeva, M.A. et al. Current Data on the Age-Related Macular Degeneration Pathophysiology: Focus on Growth Factors and Neurotrophins. Adv Gerontol 13, 105–115 (2023). https://doi.org/10.1134/S2079057024600162

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079057024600162

Keywords:

Navigation