Remote Ischemic Conditioning Protects Diabetic Retinopathy in Streptozotocin-induced Diabetic Rats via Anti-Inflammation and Antioxidation

Abstract

Ischemic conditioning inhibits oxidative stress and inflammatory response in diabetes. However, whether limb remote ischemic conditioning (LRIC) has beneficial effects on diabetic retinopathy (DR) remains unknown. This study aims to investigate the protective effects of LRIC in retinal ganglion cell in streptozotocin (STZ) induced Type 1 diabetic rats. A total of 48 healthy male Sprague-Dawley (200-220g) rats were randomly assigned to the normal group, normal+LRIC group, diabetes mellitus (DM) group and DM+LRIC group. Streptozotocin (STZ, 60 mg/kg) was intraperitoneally injected into the rats to establish the diabetic model. LRIC was conducted by tightening a tourniquet around the upper thigh and releasing for three cycles daily (10 mins x 3 cycles). Retinas were harvested after 12 weeks of LRIC treatment for histopathologic, Western blot and ELISA analysis. Plasma were collected at the same time for ELISA analysis. LRIC alleviated diabetic retinopathy symptoms as evidenced by the increased number of retinal ganglion cells (P<0.01) and decreased glial fibrillary acidic protein (GFAP) expression level (P<0.01) in the rat retina. LRIC in DM rats exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulation of pro-inflammatory cytokine: interleukin-6 (IL-6), and the up-regulation of antioxidants: superoxide dismutase (SOD), and glutathione (GSH)/oxidized glutathione (GSSG). Furthermore, LRIC significantly downregulated VEGF protein expression in the retina (P<0.01). These results suggest that the antioxidative and anti-inflammatory activities of LRIC may be important mechanisms involved in the protective effect of LRIC in STZ-induced diabetic rats.

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia

“…Notably, the expression of VEGF was also significantly decreased (P < 0:01), suggesting that ischemic PC can prevent retinal ischemia and hypoxia and delay the development of DR. Consistent with our observation, the increase of retinal VEGF expression was also noticed in rats with DM, and ischemic conditioning or pulses could significantly decrease VEGF expression [19,24].…”

“…Multiple studies using rodent models have confirmed the protective roles of PC in DM progression [19][20][21][22][23]. More recently, limb remote ischemic conditioning has been demonstrated to significantly downregulate VEGF protein expression in a rat retina through the antioxidative and anti-inflammatory activities [24]. However, the similar protective roles of PC are not studies in models with primates so far.…”

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

“…Besides, oxidative stress [5] and inflammation [6] were also pivotal for DR pathogenesis. For example, attenuation of oxidative stress by Gabapentin could help to alleviate DR in rats [7] and anti-inflammation drugs treatment attenuated DR in streptozotocin (STZ)-induced diabetic rats [8]. Hence targeting oxidative stress and inflammation might help to cure DR in clinic.…”

Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson’s Disease Severity

“…Therefore, SOD can be considered to be anti-inflammatory and anti-oxidative stress. Indeed, SOD mimetic has been successfully used to prevent the extent of inflammation (De Lazzari et al, 2018;Ren et al, 2018). As mentioned above, SOD is the prime target and the first defense mechanism of oxidative stress response upon increased cholesterol /LDL-C (Gupta et al, 2009;Dominko et al, 2018), which may prevent the inflammatory response caused by cholesterol /LDL-C to some extent.…”