Protective effect of aldehyde dehydrogenase 2 against rat corneal dysfunction caused by streptozotocin-induced type I diabetes

Aldehyde dehydrogenase 2 plays a pivotal role in detoxifying aldehydes, and our previous study revealed that aldehyde dehydrogenase 2 could alleviate diabetic retinopathy-associated damage. We aimed to characterize the potential role of aldehyde dehydrogenase 2 in diabetic keratopathy. Twenty-four rats with streptozotocin-induced (60 mg/kg, single intraperitoneal injection) type 1 diabetes mellitus (T1DM) were divided the T1DM group and the T1DM + Alda1 (an activator of aldehyde dehydrogenase 2) group (5 mg/kg/d, intraperitoneal injection, 1/2/3 months), while an additional 12 healthy rats served as the control group. Corneal morphology was examined in vivo and in vitro at one, two, and three months after T1DM induction. Additionally, serum inflammatory factors were measured by ELISA, and the expression of corneal vascular endothelial growth factor A (VEGF-A) and aldehyde dehydrogenase 2 was measured by immunofluorescence staining. Corneal cell death was evaluated by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Slit lamp analysis showed that the area of corneal epithelial cell injury in the T1DM + Alda1 group was significantly smaller than that in the T1DM group at one and two months after T1DM induction (all P < 0.05). OCT analysis and HE staining showed that the central corneal thickness (indication of corneal edema) and the epithelial keratinization level in the T1DM + Alda1 group was evidently decreased compared with those in the T1DM group (all P < 0.05). The serum inflammatory factors interleukin-1 and interleukin-6 were significantly upregulated in the T1DM group compared with the T1DM + Alda1 group at three months after T1DM induction (all P < 0.05), while there were no differences in SOD or TNF-α levels among all groups. Furthermore, corneal VEGF-A expression and corneal cell death in the T1DM + Alda1 group were dramatically reduced compared to those in the T1DM group (all P < 0.05). In conclusion, the aldehyde dehydrogenase 2 agonist Alda1 attenuated rat corneal dysfunction induced by T1DM by alleviating corneal edema, decreasing corneal cell death, and downregulating corneal VEGF-A expression.

V-Prechop nucleodissection technique feasibility in the phacoemulsification in dogs with cataracts. Clinical aspects and specular microscopy

The aim of this study was to evaluate the feasibility of the V-Prechop nucleodissection technique in the phacoemulsification in dogs and the clinical aspects and of the specular microscopy in the postoperative period. Fourty three dogs of different breeds, males and females, aged 3 to 10 years, with mature (n=22) and immature (n=21) cataracts were used. After surgery, patients were evaluated weekly for visual acuity, intraocular pressure, and endothelial corneal cell density (by non-contact specular microscopy) and quantitative flare (by laser flare photometry) during different periods. The "V-prechop" technique presented technical difficulties in implementation in patients with a mature cataract. In selected cases of patients with an immature cataract, the technique can be employed, as the nuclei are softer, allowing confection of the linear fragments in “V” to be performed. In addition, the eyes of dogs with a mature cataract presented more intensive postoperative uveitis, probably related to the greater difficulty in conducting the "V" nucleodissection. There was decreased endothelial corneal cell density in dogs with mature and immature cataracts. This occurrence was greater in patients with a mature cataract, given the increased intraocular manipulation and surgical time due to the difficulty in performing the “V” nucleodissection. According to the results obtained, the “V-prechop” nucleodissection technique can be indicated in selective cases of dogs with an immature cataract.

Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers

Relation of diabetes mellitus (DM) to the various stages of corneal nerve fiber damage is well accepted. A possible association between changes in the cornea of diabetic patients and diabetic retinopathy (DR), DM duration, and age at the time of DM diagnosis were evaluated. The study included 60 patients with DM type 1 (DM1) and 20 healthy control subjects. The density of basal epithelial cells, keratocytes and endothelial cells, and the status of the subbasal nerve fibers were evaluated using in vivo corneal confocal microscopy. Basal epithelial cell density increased with age (p=0.026), while stromal and endothelial cell density decreased with age (p=0.003, p=0.0005, p<0.0001). After the DM1 diagnosis was established, this association with age weaken. We showed nerve fiber damage in DM1 patients (p˂0.0001). The damage correlated with the degree of DR. DM1 patients with higher age at DM1 diagnosis had a higher nerve fiber density (p=0.0021). These results indicated that age at DM1 diagnosis potentially has an important effect on final nerve fiber and corneal cell density.

Application of Novel Drugs for Corneal Cell Regeneration

Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK) inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.