Abstract
Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal diseases leading to blindness. The present study explored the protective effects of hydrogen rich saline (HRS) against the photoreceptor degeneration in the N-Methyl-N-nitrosourea (MNU) administrated rat, a pharmacologically induced RP model. The therapeutic effects of intraperitoneal (IP) and intravitreous (IV) injections of HRS on regional retina was quantified via topographic measurements. The MNU administrated rats received IV or IP injections of HRS, and then they were subjected to electroretinography, multi electrode array, histological and immunohistochemistry examinations. The concentrations of the retinal malondialdehyde (MDA), superoxide dismutase (SOD), as well as the mRNA levels of apoptotic-associated genes were quantified. The IP and IV delivery pathways of HRS were both effective to ameliorate MNU induced photoreceptor degeneration. Moreover, the IV acted as a more efficient delivery method than the IP in terms of therapeutic effects. Particularly, the topographic measurements suggested that the IV delivery of HRS could alleviate MNU induced photoreceptor degeneration in the posterior retina. The immunostaining experiments also verified the comparative efficiency between IV and IP delivery of HRS on regional cone photoreceptors. Focal cone photoreceptors showed different susceptibilities to HRS and exhibited as a distinct spatial disequilibrium: cone photoreceptors in the ST quadrant were preferentially rescued; meanwhile, HRS induced protection was feeblest in the IN quadrant. Furthermore, the HRS treatment increased the level of retinal SOD, while reduce the level of retinal MDA in MNU administered rats. The expression levels of sever apoptotic -associated genes were significantly altered by HRS treatment. Collectively, these findings suggest that the IV space is an excellent target for HRS delivery. The IV delivery of HRS can efficiently alleviate the photoreceptors (especially these locate at the posterior retina) from MNU toxicity and act as a candidate treatment for RP.
Highlights
Retinitis pigmentosa comprises a heterogeneous group of hereditary retinal dystrophies that characterized by apoptotic photoreceptor death (Baumgartner, 2000)
The ERG function of the IV treated group were less impaired compared with the IP treated group: the photopic and scotopic b-wave amplitudes in the IV treated group were significantly larger than the IP treated group, indicating that the IV injection of hydrogen rich saline (HRS) could act as a more efficient delivery method to ameliorate MNU induced ERG impairments
The HRS can be delivered via IV injections, since the vitreous space is proven to be an excellent target for gene therapy and drug delivery (Wei et al, 2012)
Summary
Retinitis pigmentosa comprises a heterogeneous group of hereditary retinal dystrophies that characterized by apoptotic photoreceptor death (Baumgartner, 2000). Accumulating evidences suggest that the oxidative stress plays a significant role in retinal degeneration in both hereditary and MNU induced RP animal models (Yoshizawa et al, 1999; Rösch et al, 2014; Tao et al, 2016a). In view of the critical role of oxidative stress in the photoreceptor apoptosis, ROS might be developed into a candidate therapeutic target for RP. This notion is further reinforced by the potency of various antioxidants to ameliorate the photoreceptor degeneration in RP models (Komeima et al, 2006; Emoto et al, 2013; Wang et al, 2013; Lee et al, 2014). The surplus ROS should be eliminated instantaneously by endogenous deoxidizer or supplements with exogenous antioxidant, and otherwise they would be detrimental to retinal homeostasis
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