The effect of vitrectomy on changes in molecular biomarker levels of the vitreous cavity in the early postoperative period in proliferative diabetic retinopathy

Close metadata

PURPOSE

This study was performed to identify changes in the levels of vitreous biomarkers in patients with proliferative diabetic retinopathy (PDR) in the early postoperative period following 25-gauge vitrectomy.

MATERIAL AND METHODS

The study included 24 patients (24 eyes) with type 2 diabetes mellitus complicated by PDR requiring surgical intervention for tractional retinal detachment, subtotal or total vitreous hemorrhage, or tractional diabetic macular edema (DME). Vitreous samples were collected from all patients at the first stage of vitrectomy and one month after surgery.

RESULTS

One month after surgery, the level of the pro-inflammatory cytokine vascular endothelial growth factor (VEGF) decreased from 203.8±228.0 to 113±95 pg/ml; however, the difference was not statistically significant (p=0.307). A significant reduction was observed in the concentrations of the following pro-inflammatory biomarkers: bFGF, CTACK, Eotaxin, HGF, IL-1β, -1α, -4, -12 (p40), -16, -18, IL-2Rα, IP-10, MIG, SCF, SCGF-β, SDF-1α, MIF, and M-CSF.

CONCLUSION

The main effect of vitrectomy on pro-inflammatory cytokines is reduction of their concentration, which confirms the buffering role of the vitreous body in the accumulation of molecular biomarkers in diabetic retinopathy.

Keywords:

diabetic retinopathy

molecular biomarkers

vitrectomy

multiplex assay

Authors:

Yusef Yu.

Krasnov Research Institute of Eye Diseases;
I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID: 0000-0003-4043-456X

Petrachkov D.V.

Krasnov Research Institute of Eye Diseases

ORCID: 0000-0003-4757-5584

Baryshev K.V.

Krasnov Research Institute of Eye Diseases

ORCID: 0000-0003-0927-430X

Matyuschenko A.G.

Krasnov Research Institute Of Eye Diseases

ORCID: 0000-0002-0263-4096

Received:

10.11.2024

Accepted:

12.12.2024

List of references:

Algoritmy spetsializirovannoi meditsinskoi pomoshchi bol’nym sakharnym diabetom (11-i vypusk). Eds Dedov II, Shestakova MV, Maiorov AYu. Moscow: 2023 (In Russ.). https://doi.org/10.14341/DM13042
Klinicheskie rekomendatsii. Sakharnyi diabet: retinopatiya diabeticheskaya, makulyarnyi otek diabeticheskii. Ministerstvo zdravookhraneniya Rossiiskoi Federatsii, 2023. Accessed 30.01.2024 (In Russ.). https://cr.minzdrav.gov.ru/recomend/115_2
Konovalova KI, Shishkin MM, Fayzrakhmanov RR. Phacoemulsification of primary cataract by the second stage after vitreoretinal surgery of PDR patients. Diabetes mellitus=Sakharnyi diabet. 2020;23(5):452-458 (In Russ.) https://doi.org/10.14341/DM12256
Fimmel S, Devermann L, Herrmann A, Zouboulis C. GRO-alpha: a potential marker for cancer and aging silenced by RNA interference. Ann N Y Acad Sci. 2007; 1119:176-189. https://doi.org/10.1196/annals.1404.016
Shevchenko OP., Stakhanova EA. Multimarker (multiplex) analysis as a tool of personalized medicine. Russian Journal of Transplantology and Artificial Organs=Vestnik transplantologii i iskustvennykh organov. 2015;17(2):90-92 (In Russ.). https://doi.org/10.15825/1995-1191-2015-2-90-92
Budzinskaya MV, Plyukhova AA. Future perspectives for antiangiogenic therapy in retinal diseases. Ophthalmology in Russia=Oftal’mologiia. 2021;18(3S): 638-645 (In Russ.) https://doi.org/10.18008/1816-5095-2021-3S-638-645
Madjedi K, Pereira A, Ballios BG, Arjmand P, Kertes PJ, Brent M, Yan P. Switching between anti-VEGF agents in the management of refractory diabetic macular edema: A systematic review. Surv Ophthalmol. 2022;67(5): 1364-1372. https://doi.org/10.1016/j.survophthal.2022.04.001
Chauhan MZ, Rather PA, Samarah SM, Elhusseiny AM, Sallam AB. Current and novel therapeutic approaches for treatment of diabetic macular edema. Cells. 2022;11(12):1950. https://doi.org/10.3390/cells11121950
Cheng Y, Feng J, Zhu X, Liang J. Cytokines concentrations in aqueous humor of eyes with uveal melanoma. Medicine (Baltimore). 2019;98(5):e14030. https://doi.org/10.1097/MD.0000000000014030
Chen H, Zhang X, Liao N, Mi L, Peng Y, Liu B, Zhang S, Wen F. Enhanced expression of NLRP3 inflammasome-related inflammation in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2018;59(2):978-985. https://doi.org/10.1167/iovs.17-22816
Tang, J, Kern, TS. Inflammation in diabetic retinopathy. Progress in Retinal and Eye Research. 2011;30(5),343-358. https://doi.org/10.1016/j.preteyeres.2011.05.002
Wong TY, Cheung CMG, Larsen M, Sharma S, Simó R. Diabetic retinopathy. Nature Reviews Disease Primers. 2016;2:16012. https://doi.org/10.1038/nrdp.2016.12
Filippov VM, Petrachkov DV, Budzinskaya MV, Sidamonidze AL. Modern concepts of pathogenesis of diabetic retinopathy. Russian Annals of Ophthalmology=Vestnik Oftal’mologii. 2021;137(5-2):306-313 (In Russ.). https://doi.org/10.17116/oftalma2021137052306
Neroev VV, Zaitseva OV, Balatskaya NV, Kurchaeva ZV. Local and systemic production of VEGF-A in complicated proliferative diabetic retinopathy. Medical Immunology (Russia)=Meditsinskaja immunologija. 2016;18(4):357-364 (In Russ.). https://doi.org/10.15789/1563-0625-2016-4-357-364
Adamis AP, Shima DT, Yeo KT, Yeo TK, Brown LF, Berse B, D’Amore PA, Folkman J. Synthesis and secretion of vascular permeability factor / vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem Biophys Res Commun. 1993;193(2):631-638. https://doi.org/10.1006/bbrc.1993.1671
Aiello LP, Northrup JM, Keyt BA, Takagi H, Iwamoto MA. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol. 1995;113(12):1538-1544. https://doi.org/10.1001/archopht.1995.01100120068012
Itakura H, Kishi S, Kotajima N, Murakami M. Persistent secretion of vascular endothelial growth factor into the vitreous cavity in proliferative diabetic retinopathy after vitrectomy. Ophthalmology. 2004;111(10):1880-1884. https://doi.org/10.1016/j.ophtha.2004.03.035
Chen HJ, Ma ZZ, Li Y, Wang CG. Change of vascular endothelial growth factor levels following vitrectomy in eyes with proliferative diabetic retinopathy. J Ophthalmol. 2019;2019:6764932. https://doi.org/10.1155/2019/6764932
McAuley AK, Sanflippo PG, Hewitt AW, Liang H, Lamoureux E, Wang JJ, Connell PP. Vitreous biomarkers in diabetic retinopathy: a systematic review and meta-analysis. J Diabetes Complications. 2014;28:419-425. https://doi.org/10.1016/j.jdiacomp.2013.09.010
Laddha AP, Kulkarni YA. VEGF and FGF-2: Promising targets for the treatment of respiratory disorders. Respir Med. 2019;156:33-46. https://doi.org/10.1016/j.rmed.2019.08.003
Pepper MS, Mandriota SJ, Jeltsch M, Kumar V, Alitalo K. Vascular endothelial growth factor (VEGF)-C synergizes with basic fibroblast growth factor and VEGF in the induction of angiogenesis in vitro and alters endothelial cell extracellular proteolytic activity. J Cell Physiol. 1998;177(3):439-452. https://doi.org/10.1002/(SICI)1097-4652(199812)177:3<439::AID-JCP7>3.0.CO;2-2
Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun. 1992; 189(2):824-831. https://doi.org/10.1016/0006-291x(92)92277-5
Arrigo A, Aragona E, Bandello F. VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy. Ann Med. 2022;54(1): 1089-1111. https://doi.org/10.1080/07853890.2022.2064541
Petrachkov DV, Budzinskaya MV, Baryshev KV. Current possibilities in visualization of retinal periphery in diabetic retinopathy. Russian Annals of Ophthalmology=Vestnik Oftal’mologii. 2020;136(4):272-278 (In Russ.). https://doi.org/10.17116/oftalma2020136042272
Kociok N, Joussen AM. Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes. Graefes Arch Clin Exp Ophthalmol. 2007;245(1):101-113. https://doi.org/10.1007/s00417-006-0266-x
Kovacs K, Marra KV, Yu G, Wagley S, Ma J, Teague GC, Nandakumar N, Lashkari K, Arroyo JG. Angiogenic and infammatory vitreous biomarkers associated with increasing levels of retinal ischemia. Invest Ophthalmol Vis Sci. 2015;56:6523-6530. https://doi.org/10.1167/iovs.15-16793
Sun C, Zhang H, Jiang J, Li Y, Nie C, Gu J, Luo L, Wang Z. Angiogenic and infammatory biomarker levels in aqueous humor and vitreous of neovascular glaucoma and proliferative diabetic retinopathy. Int Ophthalmol. 2020;40:467-475. https://doi.org/10.1007/s10792-019-01207-4
Chernykh VV, Varvarinsky EV, Smirnov EV, Chernykh DV, Trunov AN. Proliferative and infammatory factors in the vitreous of patients with proliferative diabetic retinopathy. Indian J Ophthalmol. 2015;63:33-36. https://doi.org/10.4103/0301-4738.151464
Boss JD, Singh PK, Pandya HK, Tosi J, Kim C, Tewari A, Juzych MS, Abrams GW, Kumar A. Assessment of neurotrophins and infammatory mediators in vitreous of patients with diabetic retinopathy. Invest Ophthalmol Vis Sci. 2017;58:5594-5603. https://doi.org/10.1167/iovs.17-21973
Ben-Av P, Crofford LJ, Wilder RL, Hla T. Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett. 1995;372(1):83-87. https://doi.org/10.1016/0014-5793(95)00956-a
Wirostko B, Wong TY, Simó R. Vascular endothelial growth factor and diabetic complications. Prog Retin Eye Res. 2008;27(6):608-621. https://doi.org/10.1016/j.preteyeres.2008.09.002
Neroev VV, Sarygina OI, Levkina OA. Factors affecting ocular angiogenesis. Russian Annals of Ophthalmology=Vestnik Oftal’mologii. 2009;125(3): 52-54. (In Russ.).
Wang J, Chen S, Jiang F, You C, Mao C, Yu J, Han J, Zhang Z, Yan H. Vitreous and plasma VEGF levels as predictive factors in the progression of proliferative diabetic retinopathy after vitrectomy. Curr Eye Res. 2000;21(2):655-651. https://doi.org/10.1371/journal.pone.0110531

Close metadata