Evaluation of the efficacy of Dexpanthenol in experimental corneal neovascularization

The cornea is responsible for a significant portion of the eye's optical power. This optical power relies on the cornea having a transparent and avascular structure in healthy individuals. However, when the cornea is damaged for various reasons, it can lead to a serious pathology known as corneal neovascularization (CNV), which can jeopardize visual acuity. Unfortunately, an effective and safe treatment method for CNV has not been found yet. Dexpanthenol, an alcohol analogue of pantothenic acid, has been shown to have anti-inflammatory, antioxidant, anti-apoptotic, and re-epithelialization effects in experimental studies, but its impact on angiogenesis is not known. The purpose of our study is to evaluate the efficacy of dexpanthenol in an experimental corneal neovascularization model in comparison to bevacizumab. In this study, 40 female Wistar-Albino rats were utilized. Prior to the study, anterior segment examinations were conducted to confirm the absence of any damage or neovascularization in the corneas of the rats. Subsequently, corneal neovascularization (CNV) models were established by applying cauterization with silver nitrate sticks to the right eyes of the rats. On the 7th day, after confirming the presence of a significant amount of CNV in all eyes through photography, the rats were randomly divided into five groups, each containing 8 rats. The left eyes of the rats, where no procedures were performed, served as the control group. In the CNV group, no treatment was administered following cauterization. In the BSS group, 0.1 ml of balanced salt solution (BSS) was applied. The BEVA group received 2.5mg/0.1 ml bevacizumab, the DEX group received 25mg/0.1 ml dexpanthenol, and the BEVA+DEX group received a single-dose subconjunctival injection of 2.5mg/0.1 ml bevacizumab + 25mg/0.1 ml dexpanthenol. Sacrifice was performed after taking corneal photographs on the 14th day. Enucleation was applied to isolate corneal tissues from both eyes of all rats. The ratio of the CNV area in the photographs obtained on the 7th and 14th days to the total corneal area was calculated using the ImageJ program. Additionally, levels of tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor-A (VEGF-A), malondialdehyde (MDA), apoptosis, reduced glutathione (GSH), and total oxidant status (TOS) were measured in corneal tissues. When the percentage of CNV areas relative to the entire cornea was examined, it was observed that the CNV area in the CNV+BEVA and CNV+DEX groups regressed significantly compared to the CNV and CNV+BSS groups. However, the most significant regression was observed in the CNV+BEVA+DEX group. In terms of VEGF-A levels, a statistically significant decrease was noted in groups where bevacizumab and dexpanthenol were applied, compared to the CNV and CNV+BSS groups. The most notable reduction in VEGF-A levels was observed in the CNV+BEVA+DEX group. When TNF-α levels were examined, a statistically significant decrease was found in groups where bevacizumab and dexpanthenol were applied, compared to the CNV and CNV+BSS groups. The most significant decrease was observed when bevacizumab and dexpanthenol were combined. When evaluating the levels of TOS, the most significant decrease was observed in the CNV+DEX and CNV+BEVA+DEX groups. While bevacizumab application alone reduced TOS levels, the most substantial reduction was seen in the group where dexpanthenol was applied. MDA levels were examined, and the most significant decrease was found in the CNV+DEX and CNV+BEVA+DEX groups. In terms of apoptosis levels, a statistically significant reduction was observed in groups where bevacizumab and dexpanthenol were applied, compared to the CNV and CNV+BSS groups. However, the most pronounced decrease was observed when bevacizumab and dexpanthenol were administered in combination. When GSH levels were examined, the groups where dexpanthenol was applied showed a statistically significant increase in GSH levels compared to the groups without dexpanthenol application. The results indicate that in rats with the CNV model, dexpanthenol and bevacizumab significantly reduce CNV. The most effective reduction was achieved when bevacizumab and dexpanthenol were used in combination. These significant findings suggest that dexpanthenol may be a potential new agent in the treatment of corneal neovascularization. Further preclinical and clinical studies are needed to evaluate the efficacy and safety of dexpanthenol on CNV, using different doses, application timings, and methods.