Dry eye syndrome, or keratoconjunctivitis sicca (KCS), is one of the most frequent ocular disorders. It may lead to progressive corneal opacification and blindness (1). Secretory, neuronal and mechanical processes that regulate the production and mixing of tear film constituents are functionally integrated (2). The ageing process, hormonal, environmental, iatrogenic, pharmacological and pathogenic factors may disrupt the tear film with subsequent ocular surface inflammation (3). The hyperosmolar tear film stimulates the production of mitogen-activated protein kinase (4). This initiates a cascade of protein phosphorylation involving other kinases and nuclear transcription factors which stimulate the proinflammatory cytokines and chemokines in tear fluid and conjunctival epithelium in KCS (5). The purpose of this study was to compare the topical anti-inflammatory effects of the nonselective cyclooxygenase (COX) inhibitor, ketorolac, with the selective COX-2 inhibitor, nimesulide, in an animal model of dry eye in albino rabbits. All animals were examined by the Schirmer test, tear break-up time (TBUT) and fluorescein corneal staining test. Dry eye model showed significant reduction in tear volume, TBUT, corneal staining and histopathological signs of dryness and inflammation. On treating dry eye model with nimesulide 0.1% eye drops and ketorolac 0.5% eye drops, there were improvements in Schirmer test values, TBUT and fluorescein corneal staining and histopathologically reduced inflammatory reaction, with signs of healing and regeneration. Both nimesulide and ketorolac ameliorate atropine sulphate induced dry eye in albino rabbits. The use of selective COX-2 inhibitor, nimesulide, is preferred to avoid local and systemic side effects which may occur with the use of the nonselective COX inhibitor, ketorolac.

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Background: Imbalance between protein synthesis and endoplasmic reticulum (ER) capacity to modify and fold proteins lead to the accumulation of unfolded proteins resulting in ER stress and apoptosis. Chaperones are major defense molecules assisting in protein folding, transport, and cellular signaling. ER stress plays a major role in the pathogenesis of diabetes mellitus (DM) and its complications, e.g., diabetic cataract. In the present investigation, the chemical chaperones 4-phenylbutyric acid (4-PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO) are used as potential therapeutic agents for alleviation of DM-induced ER stress and diabetic cataract in rats. Animals are subjected to biochemical analysis of blood and lenses for ER stress and apoptosis markers. Moreover, ophthalmologic examination and histopathologic examination of the lenses were done to confirm the results. Results: Both ophthalmic and lens histopathologic examination revealed that treatment with 4-PBA and TUDCA retarded the occurrence of cataract markedly. Whereas, treatment with TMAO caused a partial improvement of cataract. Moreover, biochemical tests showed that both 4-PBA and TUDCA produced a remarkable improvement in the ER marker levels (VEGF and caspase-12), GSH, MDA, TAC levels in lens tissues. On the other hand, TMAO had no significant effect on these parameters. However, Western blot analysis of lens homogenates showed a suppressed expression of GRP78 and CHOP after treatment with 4-PBA, TUDCA, and TMAO. Moreover, all treated groups showed a significant improvement of lens soluble proteins and their UV spectra absorption. A significant improvement in fasting blood sugar, GSH, serum MDA, and TAC were noted in all treated groups. 4-PBA produced a significant decrease in insulin resistance, whereas TUDCA and TMAO showed insignificant change. Conclusion: The present research found that the tested chaperones could be used as a therapeutic approach for clinically relevant disorders featuring ER dysfunction such as DM and for reducing its complications in the eye mainly cataract. However, TUDCA and 4-PBA were found to have a more potential efficacy in reducing most of the tested parameters as compared to TMAO.

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