Intraocular tumour necrosis factor ligand related molecule 1 A links disease progression of proliferative diabetic retinopathy after primary vitrectomy

Tumour necrosis factor ligand related molecule 1 A (TL1A), a member of tumour necrosis factor superfamily, has been identified as a crucial regulator for vascular homeostasis and inflammation. However, the function of TL1A in diabetic retinopathy (DR) is largely unknown. This study aims to examine levels of TL1A in serum and intraocular fluid in patients with proliferative diabetic retinopathy (PDR), and to explore the correlation of intraocular TL1A with the prognosis of PDR progression after primary vitrectomy. Seventy-five patients (75 eyes) with PDR who underwent pars plana vitrectomy (PPV) and 19 patients (19 eyes) who received vitrectomy for idiopathic macular holes (IMH) as non-diabetic control group were enrolled in this prospective study. Serum, aqueous and vitreous fluid samples were collected during cataract and PPV surgery. Protein expressions of TL1A as well as other angiogenic and inflammatory cytokines in serum and intraocular fluid were measured. Correlations of intraocular TL1A concentrations with inflammatory cytokines were analyzed. We found both aqueous and vitreous TL1A levels were significantly higher in the PDR group than in control group (P_aqueous = 0.026; P_vitreous <0.001). Angiogenic and inflammatory cytokines such as VEGF, IL-6, IL-8, MCP-1, MIP-1α, and MIP-1β were significantly higher in intraocular fluid in PDR group than in controls, which MCP-1 and MIP-1α showed positive correlation with intraocular TL1A levels. There is no significant difference in the levels of serum TL1A as well as other inflammatory cytokines between PDR patients and controls. Intraocular levels of TL1A were significantly lower in PDR progression group than in the stable group (P_aqueous <0.001; P_vitreous <0.001). Multivariate logistic regression analyses revealed that lower levels of intraocular TL1A was an important risk factor for predicting PDR progression after primary PPV (OR_aqueous = 0.717, P_aqueous = 0.001; OR_vitreous = 0.684; P_vitreous = 0.002). In conclusion, TL1A and multiple inflammatory cytokines were highly enriched in the intraocular fluid of PDR patients compared with the controls. Lower levels of intraocular TL1A were associated with development of PDR complications after primary PPV and might be used as prognostic factor in predicting the vitrectomy outcome in PDR patients.