Background: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections. Methods: Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations. Results: The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups (p < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group (p < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them. Conclusions: Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model.

This study aims to investigate the anatomical differences in the anterior segment of the eyes between dogs and cats using ultrasound biomicroscopy (UBM) to understand the higher prevalence of primary angle-closure glaucoma (PACG) in dogs compared to cats. Retrospective analysis was performed on clinical data from 16 eyes of 16 dogs and 14 eyes of 14 cats with normal eye conditions. UBM was utilized to measure nine specific parameters, including Schwalbe’s Line Distance (SLD), Iridocorneal Angle (ICA), Angle-Opening Distance (AOD), and three ciliary cleft parameters: width (CCW), length (CCL), and area (CCA). To account for differences in body size, ciliary cleft parameters were adjusted accordingly. Significant anatomical differences in the anterior segment were found between the two species. Dogs had smaller values for SLD, ICA, AOD, and ciliary cleft parameters (CCW, CCL, CCA) compared to cats. Even after body-size adjustment, the rectified ciliary cleft parameters remained smaller in dogs. The anatomical differences, particularly the smaller ciliary cleft and narrower drainage angles in dogs, may contribute to the higher prevalence of PACG in this species. Conversely, the larger ciliary cleft in cats may explain the lower occurrence of primary glaucoma in cats.

Diabetic retinopathy (DR) is a microvascular and retinal neurologic disorder that occurs in patients with long-term diabetes. Umbilical cord blood-derived mesenchymal stem cell (UCB-MSC) therapy has emerged as a promising treatment because of its regenerative potential; however, its effectiveness is limited under hyperglycemic conditions, which results in the overproduction of mitochondrial reactive oxygen species (mtROS), leading to cellular senescence. In this study, we examined the potential of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, to enhance the efficacy of MSCs in a high glucose environment, which is typical of DR. Increased glucose levels enhanced glucose uptake, primarily through glucose transporter 3 (GLUT3) overexpression, which resulted in the excess generation of mtROS and ultimately induced cell death. Everolimus inhibited intracellular glucose levels and mtROS production, and increased the survival of MSCs under high glucose conditions. Everolimus also inhibited mTORC1, which resulted in reduced actin stabilization and decreased membrane translocation of GLUT3. This effect was associated with the down-regulation of cofilin phosphorylation, a key factor in actin dynamics, which further suppressed high glucose-induced glucose influx and mtROS generation. Furthermore, the results of the streptozotocin (STZ)-induced DR rat model indicated that the groups receiving a subconjunctival injection of GLUT3 knockdown or everolimus-pretreated UCB-MSCs in STZ rats showed improved retinal function compared with the untreated DR groups. Taken together, the results suggest that everolimus enhances the viability and function of UCB-MSCs under hyperglycemic conditions by modulating glucose homeostasis and reducing oxidative stress. This represents a novel therapeutic strategy for the treatment of DR.