There is growing evidence that chronic inflammation plays a role in both the development and progression of diabetic retinopathy. There is also evidence that molecules produced as a result of hyperglycemia can activate microglia. However the exact contribution of microglia, the resident immune cells of the central nervous system, to retinal tissue damage during diabetes remains unclear. Current data suggest that dysregulated microglial responses are linked to their deleterious effects in several neurological diseases associated with chronic inflammation. As inflammatory cytokines and hyperglycemia disseminate through the diabetic retina, microglia can change to an activated state, increase in number, translocate through the retina, and themselves become the producers of inflammatory and apoptotic molecules or alternatively exert anti-inflammatory effects. In addition, microglial genetic variations may account for some of the individual differences commonly seen in patient's susceptibility to diabetic retinopathy.

The visual processing of humans is primarily reliant upon the sensitivity of cone photoreceptors to light during daylight conditions. This underscores the importance of understanding how cone photoreceptors maintain the ability to detect light. The vertebrate retina consists of a combination of both rod and cone photoreceptors. Subsequent to light exposure, both rod and cone photoreceptors are dependent upon the recycling of vitamin A to regenerate photopigments, the proteins responsible for detecting light. Metabolic processing of vitamin A in support of rod photopigment renewal, the so-called "rod visual cycle", is well established. However, the metabolic processing of vitamin A in support of cone photopigment renewal remains a challenge for characterization in the recently discovered "cone visual cycle". In this review we summarize the research that has defined the rod visual cycle and our current concept of the novel cone visual cycle. Here, we highlight the research that supports the existence of a functional cone-specific visual cycle: the identification of novel enzymatic activities that contribute to retinoid recycling, the observation of vitamin A recycling in cone-dominated retinas, and the localization of some of these activities to the Müller cell. In the opinions of the authors, additional research on the possible interactions between these two visual cycles in the duplex retina is needed to understand visual detection in the human retina.

Using streptozotocin-induced diabetic Wistar rats, studies were camed out to examine the metabolic availability of vitamin A in the plasma, liver and the retina of the eye. Control and diabetic rats were fed ad lib. on a semi-puriiied diet either with or without (basal) vitamin A supplementation, or pair-fed on the basal diet for 4 weeks. Despite the fact that diabetic rats consumed 48 YO more feed, they had lower plasma concentrations of retinol (P < 0.003). The decrease in plasma retinol concentration was a response to diabetes (or diabetes-induced trauma), since neither pair-feeding ( P < 0.01) nor vitamin A supplementation altered this effect (P < 0.05). Furthermore, the hepatic concentrations of the vitamin in these animals remained elevated and this increase was greater in the supplemented diabetic group ( P < 0.001). Decreases in 1 1 4 s retinal (a component of rhodopsin) concentrations in the retina were also observed in diabetic animals. The increased hepatic and the decreased plasma and retina vitamin A levels suggest a defect in the transport of the vitamin from the liver. Diabetes: Streptozotocin: Vitamin A

Bioprinting is an additive manufacturing technology with great potential in medical applications. Among available bioprinting techniques, laser-assisted bioprinting (LAB) is a promising technique due to its high resolution, high cell viability, and the capability to deposit high-viscousity bioink. These characteristics allow the LAB technology to control cells precisely to reconstruct living organs. Recent developments of LAB technologies are reviewed in this paper, covering various designs of LAB printers, re-search progresses in energy-absorbing layer (EAL), the physical phenomenon that triggers the printing process in terms of bubble formation and jet development, printing process parameters, and major factors related to the post-printing cell viability. The latest studies on LAB technologies are highlighted, expounding their advantages and disadvantages, and some potential applications are presented. The potential technical challenges and future research trends for LAB technologies are also discussed.

Retinal pigment epithelial (RPE) cells secrete vascular endothelial growth factor (VEGF), a cytokine known to promote angiogenesis. Results from RNase protection assays (RPAs) show that RPE from non-diabetic human donors and from adult retinal pigment epithelium-19 (ARPE-19) cells expressed significant bone morphogenetic protein-4 (BMP-4) message. In addition, ARPE-19 cells cultured in high glucose (25 mM), compared to those in physiological glucose (5.5 mM) released significantly more BMP-4 into the conditioned media (CM). However, the effect of BMP-4 on the release of VEGF by ARPE-19 cells has not been studied. Accordingly, ARPE-19 cells were treated with BMP-4 to determine VEGF secretion. BMP-4 and VEGF levels in the CM and cell lysates were measured by enzyme-linked immunosorbent assay (ELISA). Cells treated with exogenous BMP-4 had higher VEGF in the CM and this treatment effect was dose-and timedependent, while cell lysates had low levels of VEGF. Addition of cycloheximide (CHX) or actinomycin-D (ACT) significantly reduced VEGF secretion from cells treated with BMP-4, suggesting that the BMP-4-induced secretion of VEGF requires new RNA and protein synthesis. Our results suggest that BMP-4 may play a role in the regulation of ocular angiogenesis associated with diabetic retinopathy (DR) by stimulating VEGF release from RPE cells.