There is growing evidence that the pathogenesis of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) have a significant chronic inflammatory component. A vital part of the inflammatory cascade is through the activation of pattern recognition receptors (PRR) such as toll-like receptors (TLR). Here, we reviewed the past and current literature to ascertain the cumulative knowledge regarding the effect of TLRs on the development and progression of retinal diseases. There is burgeoning research demonstrating the relationship between TLRs and risk of developing retinal diseases, utilising a range of relevant disease models and a few large clinical investigations. The literature confirms that TLRs are involved in the development and progression of retinal diseases such as DR, AMD, and ischaemic retinopathy. Genetic polymorphisms in TLRs appear to contribute to the risk of developing AMD and DR. However, there are some inconsistencies in the published reports which require further elucidation. The evidence regarding TLR associations in retinal dystrophies including retinitis pigmentosa is limited. Based on the current evidence relating to the role of TLRs, combining anti-VEGF therapies with TLR inhibition may provide a longer-lasting treatment in some retinal vascular diseases.

OBJECTIVE: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies.
METHODS: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography.
RESULTS: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl3. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion.
CONCLUSIONS: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR.

OBJECTIVE: To study the retinal oxygen saturation in normal eyes of Chinese adolescents.
METHODS: Performing retinal oximetry with the Oxymap T1 Retinal Oximeter in healthy children and adolescents (aged 5-18 years old), we measured the arterial (SaO2 ) and venular (SvO2 ) oxygen saturation and the arteriovenous difference in oxygen saturation (Sa-vO2 ).
RESULTS: The study included 122 individuals with a mean age of 13.0 ± 2.9 years (range: 5-18 years) and a mean refractive error of -3.25 ± 2.49 dioptres (range:-8.88 to +3.13 dioptres). Mean SaO2 , SvO2 and Sa-vO2 was 85.5 ± 7.1%, 48.2 ± 5.5% and 37.3 ± 6.5%, respectively. Mean SaO2 was significantly (p < 0.001) the lowest in the inferotemporal quadrant (79.1 ± 9.0%), followed by the superotemporal quadrant (83.4 ± 9.7%), the inferonasal quadrant (90.4 ± 10.6%) and the superonasal quadrant (93.4 ± 10.8%). In a similar manner, the values of the SvO2 were the lowest (p < 0.001) in the inferotemporal quadrant (42.1 ± 8.3%), followed by the superotemporal quadrant (47.8 ± 7.2%), the inferonasal quadrant (52.3 ± 8.4%) and the superonasal quadrant (55.1 ± 7.6%). Arteriovenous difference in oxygen saturation (Sa-vO2 ) did not differ significantly (all p > 0.05) between the fundus quadrants. In multiple linear regression analysis, SaO2 increased (regression coefficient r2  = 0.28) with older age (standardized regression coefficient β: 0.23; p = 0.01) and more myopic refractive error (β: -0.39; p < 0.001). Higher SvO2 was significantly correlated with more myopic refractive error (β: -0.46; p < 0.001; r2  = 0.20), while Sa-vO2 increased significantly only with older age in the multivariate analysis (β: 0.26; p = 0.01; r2  = 0.07).
CONCLUSIONS: Our study provides normative data for Chinese children and adolescents who showed lower values than adults for SaO2 and SvO2 . SaO2 increased with older age and higher myopic refractive error, SvO2 increased with higher myopic refractive error, and Sa-vO2 increased with older age.