Immunological biomarkers of the vitreous responsible for proliferative alteration in the different forms of retinal detachment

Abstract

Background The purpose of the study was to explore the immunological components that are responsible for the proliferative alterations in the different forms of retinal detachment (RD). Methods Vitreous fluids were collected during 23G pars plana vitrectomy from 54 eyes of 54 patients with different RD types, such as rhegmatogenous RD (RRD) without proliferative vitreoretinopathy (PVR) (n = 30), PVR (n = 16) and proliferative diabetic retinopathy (PDR) with tractional RD (n = 8). Vitreous fluids were obtained from 19 eyes with epiretinal membrane (ERM), which were used as control samples. A multiplex chemiluminescent immunoassay was performed to evaluate the concentrations of 48 cytokines, chemokines and growth factors. Results The expression levels of eotaxin, IFN-gamma, IL-6, IL-8, IL-16, MCP-1, MIF and MIP-1 beta were significantly higher in all RD groups than in the ERM group. The levels of CTACK, IP-10, SCGF-beta, and SDF-1 alpha were significantly higher in patients with diabetic tractional RD and PVR than in other patients. The upregulation of VEGF and IL-18 was detected in PDR. Conclusions Our results indicate that complex and significant immunological mechanisms are associated with the pathogenesis of different forms of RD: selected cytokines, chemokines and growth factors are upregulated in the vitreous of eyes with RD. The detected proteins are present in different concentrations both in RRD and PVR. In the presence of PVR and PDR, the majority of cytokines are upregulated; thus, they may serve as biomarkers to estimate the progression or severity level of proliferation and later to develop personalized therapeutic strategies to slow down or prevent pathological changes.

Upregulation of Neuroinflammatory Protein Biomarkers in Acute Rhegmatogenous Retinal Detachments

“…IL-8 is produced by phagocytes and mesenchymal cells and activates, recruits, and promotes extravasation and the respiratory burst of neutrophils. Several studies suggest that chemoattraction and neutrophils are involved in the retinal detachment and PVR disease processes [ 20 , 22 ]. Furthermore, Takahashi et al hypothesized that IL-8 levels could reflect the level of photoreceptor damage given that IL-8 was found to be positively correlated with the extent of detachment, and photoreceptor cell damage indirectly increases IL-8 expression [ 23 ].…”

“…Similarly, MIP-1β promotes the migration and adhesion of macrophages and microglia [ 58 , 59 ]. Additionally, IP-10 is a pro-inflammatory chemoattractant for monocytes and macrophages and functions as an anti-angiogenic and antifibrotic agent ( Table A2 ) [ 20 , 21 , 22 ]. Therefore, while IP-10 may attract leukocytes to the inflamed area of retinal detachment, it may also counteract the fibrotic actions of MCP-1 and MIP-1β as proposed by Takahashi et.…”

“…Previous studies have found elevated levels of inflammatory cytokines in patients with RRD; however, the reported cytokine profiles are variable, and the lack of consistency in the data warrants further study ( Table A1 and Table A2 ) [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Translational and clinical advancements in management of proliferative vitreoretinopathy

“…A recent study applying proteomic analysis of preretinal PVR membranes identified ECM organization and extracellular structure organization as two pathways that were enriched in PVR [61]. Another study analyzing vitreous cytokines, chemokines, and growth factors in eyes undergoing vitrectomies identified elevated levels of CTACK, IP-10, SCGF-beta, and SDF-1 alpha in patients with PVR and diabetic tractional RDs [62 ▪ ]. A study identified Myo/Nog cells, which are involved in fibrosis, for the first time in preretinal membranes from patients with traumatic PVR RDs [63].…”

Proliferatív vitreoretinopathia

“…Kórélettani szempontból citokinek, kemokinek és növekedési faktorok komplex együtthatása alakítja ki a kórfolyamatot (4. ábra, 3. táblázat). A molekulák részletes leírása meghaladná jelen közlemény kereteit, a 4. ábrán igyekeztünk kiemelni a legfontosabb patomechanizmusokat (4,5). Részletes elemzés olvasható többek között Chaudhary közleményében (10).…”