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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.

Purpose: To stress the influence of Coenzyme Q10 (CoQ10) on the structural properties of liposomes as model membranes and to investigate the possible role of CoQ10 or CoQ10 doped in liposomes when topically instilled as eye drops, in preventing cataract.Methods: The molecular interaction between liposomes and Coenzyme Q10 was examined using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Rat pups were randomly divided into six groups comprising 15 pups. Group (1), control group. Group (2), untreated model of cataract, received a single subcutaneous injection of sodium selenite. Instillation of pure CoQ10 (Group 3), CoQ10 encapsulated into neutral (Group 4), positive (Group 5) and negative (Group 6) Dipalmitoyl phosphatidylcholine (DPPC) liposomes on the opacification of lenses in rat pups after sodium selenite injection was topically received.Results: The incorporated CoQ10 is probably associated with lipid bilayers where it interacts to a large extent and perturbs them. This results in strong broadening and shift to lower temperature (94°C) of the major characteristic endothermic peak of pure DPPC at 105°C. FTIR showed that the incorporation of CoQ10 into DPPC induces a conformational change in the polar region of DPPC. Ophthalmological and Biochemical studies revealed that CoQ10 alone followed by negatively charged liposomes doped with CoQ10 are more effective in reducing the progress of cataract as well as improving the lens soluble proteins levels and total antioxidant capacity.Conclusion: The interactions of CoQ10 with membrane systems may contribute to a better understanding of CoQ10 physiological properties and the development of therapeutically advanced systems.

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