Possible association of primary open-angle glaucoma with thyroid dysfunction and oxidative stress

Background Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Thyroid dysfunction and oxidative stress can be associated with POAG. Purpose The aim of this study was to determine whether thyroid dysfunction (hypothyroidism or hyperthyroidism) is associated with glaucoma in Egyptian patients and to evaluate the level of oxidative stress (OS) markers in the serum of POAG patients. It also aimed to investigate the relationship between the OS markers and thyroid hormones in those patients. Patients and methods The study included 60 patients with POAG who were compared with 20 normal controls. Serum samples from the POAG patients and controls were examined for thyroid hormones [triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH)] using the ELISA technique. The OS markers [hydrogen peroxide (H2O2), nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH)] were also determined using colorimetric methods. Results There were no significant differences in the levels of T4 and TSH in the patients (3.14±2.25 ng/dl and 2.43±1.37 u/l, respectively) compared with the controls (3.35±1.88 ng/dl and 1.76±0.99 u/l, respectively) (P=0.245 and 0.064, respectively). However, there was a significant decrease in the T3 level in the POAG patients (2.88±0.54 pg/ml) compared with the controls (3.35±0.6 pg/ml) (P=0.029). In addition, there was a significant increase in the levels of H2O2 (2.83±1.66 mM/l), NO (54.64±29.21 umol/l), and MDA (164.12±96.5 nmol/ml) in the patients compared with the controls (0.83±0.55 mMol/l, 22.49±6.37 umol/l, and 44.36±12.59 nmol/ml, respectively) (P<0.001). There was also a significant decrease in the level of GSH in patients (54.32±32.1 mg/dl) compared with controls (103.99±45.52 mg/dl), (P<0.001). A significant negative correlation was detected between TSH and T4 (r=−0.41, P= 0.001), TSH and MDA (r=−0.27, P=0.04), T3 and H2O2 (r=−0.05, P=0.05), and T4 and NO (r=−0.35, P=0.01). Conclusion There was no association between POAG and thyroid dysfunction. However, the POAG patients are susceptible to OS and damage, as they had elevated serum levels of H2O2, NO, and MDA and reduced levels of GSH. Since the thyroid hormone level was associated with the OS markers, antioxidant therapy may be beneficial and may help to regulate the intraocular pressure and protect the trabecular meshwork cells from OS in those patients

Potential prophylactic effect of chemical chaperones for alleviation of endoplasmic reticulum stress in experimental diabetic cataract

Abstract 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