Kovalchuk Kh. V.

GEOGRAPHIC ATROPHY IN PATIENTS WITH DRY AGE-RELATED MACULAR DEGENERATION: CURRENT PROBLEMS OF PATHOGENESIS AND PROSPECTS FOR PROGRESSION DIAGNOSTICS


About the author:

Kovalchuk Kh. V.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

Geographic atrophy (GA) of the retinal pigment epithelium (RPE) of the retina is a severe complication of age-related macular degeneration (AMD), which leads to progressive and irreversible loss of visual function. Aim of this study: to investigate new links of pathogenesis and perspectives of diagnostics of geographical atrophy progression in patients with dry form of age-related macular degeneration. Object and methods. The study was prospective and included 74 patients (136 eyes) with early and intermediate stages of dry form of AMD in accordance with the present study. Ophthalmic examination included visual acuity, visual fields, tonometry, gonioscopy, biomicroscopy, ophthalmoscopy, optical coherence tomography. To study the functional activity of platelets (PL) receptors, agonists were used: ATP, ADP, adenosine, TC activation factor (FAT), adrenaline and isadrine. Estimation of PL aggregation was performed by the turbidimetric method. Results. Comparison of PL receptors reactivity in patients with early stage dry form of AMD showed that the development of dystrophic changes was characterized by an increase in the reactivity of purine P2Y- and P2Xreceptors (p <0.01), α2-adrenoceptors (p <0.01) and FAT receptors (p <0.01). The decrease in the activity of A2A receptors and β2-adrenoceptors (p <0.001) reflected the lack of efficiency of existing vasodilator and cytoprotective mechanisms. In patients with intermediate stage of dry form of AMD, in which there were multiple medium-sized druzen associated with GA, preservation of hyperreactivity of purine receptors (P2Y- and P2X-), α2-adrenoceptors and FAT PL receptors; ADP provided increased PL aggregation (p <0.01); the PL response to adenosine and isadrine decreased (p <0.001). Conclusions. Thus, the reactivity of PL receptors reflects the influence of the pathogenetic factors of AMD, and therefore can be used to predict the risk of developing GA in such patients.

Tags:

age-related macular degeneration, geographical atrophy, retinal pigment epithelium, platelet receptors, pathogenesis, diagnostics.

Bibliography:

  1. Plyukhova AA, Budzinskaya MV. The role of anti-VEGF therapy in geographic atrophy progression. Vestn Oftalmol. 2018;134(5.2):289-93.
  2. Grassmann F, Harsch S, Brandl C, Kiel C, Nürnberg P, Toliat MR, et al. Assessment of Novel Genome-Wide Significant Gene Loci and Lesion Growth in Geographic Atrophy Secondary to Age-Related Macular Degeneration. JAMA Ophthalmol. 2019 May 23. DOI: 10.1001/ jamaophthalmol.2019.1318
  3. Reigada D, Zhang X, Crespo A, Nguyen J, Liu J, Pendrak K, et al. Stimulation of an alpha1-adrenergic receptor downregulates ecto-5’ nucleotidase activity on the apical membrane of RPE cells. Purinergic Signal. 2006;2(3):499-507.
  4. Alagorie AR, Verma A, Nassisi M, Sadda SR. Quantitative assessment of choriocapillaris flow deficits in eyes with advanced age-related macular degeneration versus healthy eyes. Am J Ophthalmol. 2019 Sep;205:132-9. DOI: 10.1016/j.ajo.2019.04.037
  5. Thulliez M, Zhang Q, Shi Y, Zhou H, Chu Z, de Sisternes L. Correlations between choriocapillaris flow deficits around geographic atrophy and enlargement rates based on swept-source oct imaging. Ophthalmol Retina. 2019;3(6):478-88.
  6. Burnstock G. Purinergic Signaling in the Cardiovascular System. Circ Res. 2017;120(1):207-28.
  7. Geldenhuys WJ, Hanif A, Yun J, Nayeem MA. Exploring adenosine receptor ligands: potential role in the treatment of cardiovascular diseases. Molecules. 2017;22(6). DOI: 10.3390/molecules22060917
  8. Arsyad A, Dobson GP. Adenosine relaxation in isolated rat aortic rings and possible roles of smooth muscle Kv channels, KATP channels and A2a receptors. BMC Pharmacol Toxicol. 2016;17(1):23.
  9. Kolomeyer AM, Maguire MG, Pan W, VanderBeek BL. Systemic beta-blockers and risk of progression to neovascular age-related macular degeneration. Retina. 2019;39(5):918-25.
  10. Quinn RH, Quong JN, Miller SS. Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2001;42(1):255-64.
  11. Guha S, Liu J, Baltazar G, Laties AM, Mitchell CH. Rescue of compromised lysosomes enhances degradation of photoreceptor outer segments and reduces lipofuscin-like autofluorescence in retinal pigmented epithelial cells. Adv Exp Med Biol. 2014;801:105-11.
  12. Kokkinaki M, Abu-Asab M, Gunawardena N, Ahern G, Javidnia M, Young J, еt al. Klotho regulates retinal pigment epithelial functions and protects against oxidative stress. J Neurosci. 2013;33(41):16346-59.
  13. Reichenbach A, Bringmann A. Purinergic signaling in retinal degeneration and regeneration. Neuropharmacology. 2016;104:194-211.
  14. Fowler BJ, Gelfand BD, Kim Y, Kerur N, Tarallo V, Hirano Y, et al. Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity. Science. 2014;346(6212):1000-3.
  15. Relvas LJ, Bouffioux C, Marcet B, Communi D, Makhoul M, Horckmans M, et al. Extracellular nucleotides and interleukin-8 production by ARPE cells: potential role of danger signals in blood-retinal barrier activation. Invest Ophthalmol Vis Sci. 2009;50(3):1241-6.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 4 Part 2 (154), 2019 year, 107-111 pages, index UDK 617.736-007.17-053-092.12

DOI: