Informativeness of multiplex flow cytometry in the study of the balance of pro-and antiangiogenic growth factors in vitreous fluid in neovascular age-related macular degeneration
Authors:   A.I. Burnazyan Federal Biophysical Center of FMBA of Russia, Moscow, Likhvantseva V.G. ,   Academy of Postgraduate Education of the Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of FMBA of Russia, Moscow, Gevorgyan A.S. ,   Academy of Postgraduate Education of the Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of FMBA of Russia, Moscow, Kapkova S.G. ,   A.I. Burnazyan Federal Biophysical Center of FMBA of Russia, Moscow,   Academy of Postgraduate Education of the Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of FMBA of Russia, Moscow, Rychkova S.I. ,   A.I. Burnazyan Medical-Biological University of Innovation and Continuing Education, Federal MedicalBiological Agency, Moscow, Arkhipova M.M. ,   Central Clinical Hospital of the Russian Academy of Sciences, Moscow, Selkov S.A. ,   FGBU “Research Institute of Obstetrics, Gynecology and Reproduction named after D. O. Ott”, St. Petersburg
Published: June 2022

Aim: to study the level of pro- and antiangiogenic growth factors in vitreous fluid in neovascular AMD. Methods. The concentration of proangiogenic (IL-8, angiogenin, TNFα, VEGF, bFGF) and antiangiogenic (IFNα, TGFβ, IFNγ) growth factors in the vitreous fluid of 24 patients with the neovascular form of age-related macular degeneration (nAMD) was determined by multiplex flow cytometry; 38 patients with senile cataracts without signs of AMD served as a matching group. Results. In nAMD compared to senile cataracts, proangiogenic cytokines TNFα were present more often and at a higher level in the vitreous fluid (75 vs. 47.5 %, p < 0.05; M±m: 2.36±0.46 vs. 1.35±0.30 pg / ml, p < 0.05), IL-8 (100 vs. 75 %, p < 0.01; 492.87±75.7 vs. 8.48±1.5 pg/ml, p < 0.01), angiogenin (3822.4±498.57 vs. 2820.15±319.27, p < 0.01) and FGFb (58.3 vs. 26.7 %, p < 0.05; M±m: 10.05±5.93 vs. 2.72±1.04, p < 0.01). In both groups of patients, antiangiogenic factors IFNγ and TGFβ were practically not detected, but the concentration of IFNα was significantly higher (6.42±1.71 versus 4.42±0.41, p < 0.01). VeGF levels in both nosological groups were almost identical: M±m: 17.48±13.97 (with nAMD) versus 18.44±3.23 (n/s), while the frequency of its detection in the cataract group was significantly higher (68.2 % vs. 17 %, p < 0.01). By way of explanation, it can be assumed that since patients with nAMD had previously been administered the anti-angiogenic drug ranibizumab, it is possible that the VEGF production was under the control of the drug (suppressed). Conclusions. 1. Elevated levels of proangiogenic growth factors IL-8, angiogenin, TNFα and bFGF in vitreous fluid in nAMD against the background of antiangiogenic therapy with Lucentis suggest the presence of other, non-VEGF-independent mechanisms for stimulating angiogenesis. 2. The absence of antiangiogenic growth factors IFNγ and TGFβ in the vitreous fluid allows to think about the presence of a defect in the control and regulation of angiogenesis in nAMD. 3. Rare detection of VEGF in combination with a significant decrease in its concentration compared to senile cataracts against the background of treatment with ranibizumab of the eyes with nAMD demonstrates targeted inhibition in practice. Key words: age-related macular degeneration; growth factors; vitreous fluid; angiogenesis; antiangiogenic therapy