Clinical and molecular markers in retinal detachment—From hyperreflective points to stem cells and inflammation

Abstract

Purpose Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment. Methods 12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin). Results OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer—their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo , the SRF doubled their capacity for engulfing dying RPEs. Conclusions Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.

Changes in Retinal Vessel and Retinal Layer Thickness After Vitrectomy in Retinal Detachment via Swept-Source OCT Angiography

“…25 Although the causal relationship between decreased CCP blood flow and the defect of the photoreceptor layer in macula-off RRD could not be elucidated in this retrospective study, studies have shown that the subretinal fluid (SRF) contains inflammatory cytokines and other factors that contribute to triggering and enhancing the inflammatory and immune responses. 26,27 The bloodretina barrier may also get damaged during RD, similar to the RPE cells, 28,29 and vasoconstrictors, such as endothelin, are known to be present in the SRF. 30,31 Taken together, we could hypothesize that, after RRD occurred, the detached neurosensory retina might be damaged by inflammatory cytokines in the SRF, and CCP blood flow might be impaired because of such cytokines.…”

Position of macula lutea and presence of proliferative vitreoretinopathy affect vitreous cytokine expression in rhegmatogenous retinal detachment

“…They found that 37 of the studied cytokines were significantly higher in the subretinal fluid of RRD patients compared to the vitreous of non-RRD patients. [36] Our study has some limitations, such as the complexity and a high number of cytokines that need further investigations to detect their relationships more exactly. Retinal detachments present with variable clinical features, which might contribute to the multiplex variations of cytokines in the fluids.…”

Preoperative, Intraoperative and Postoperative Corticosteroid Use as an Adjunctive Treatment for Rhegmatogenous Retinal Detachment

“…There is increasing evidence that in the presence of RRD, the activation of inflammatory processes occurs, in particular when it is associated with choroidal detachment [5,6]. The surgeries themselves, both scleral buckle (SB) and pars plana vitrectomy (PPV), induces an inflammatory response as demonstrated by an increase of aqueous flare values, from day one up to three months post-operatively with the peak value observed at post-operative day seven [7].…”