Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are the major factors underlying photoreceptor degeneration. Lutein, RR-zeaxanthin (3R,3’R-zeaxanthin) and RS (meso)-zeaxanthin (3R,3’S-RS- zeaxanthin) (L/Zi) could protect against cell damage by ameliorating OS in retina. In this study, we examined the effect of L/Zi supplementation in a mouse model of photoreceptor degeneration and investigated whether the treatment of L/Zi ameliorated OS and ERS. BALB/cJ mice after light exposure were used as the animal model. The protective effects of L/Zi were observed by electroretinography (ERG) and terminal deoxyuridine triphosphate nick-end labeling (TUNEL) analysis. The underlying mechanisms related to OS and ERS were explored by Western blotting. After L/Zi treatment, the ERG amplitudes were significantly higher, and the number of TUNEL-positive cells was significantly reduced compared to that of the vehicle group. Western blotting results revealed that OS was ameliorated according to the significant downregulation of phosphorylated c-Jun N-terminal kinase (p-JNK), and significant upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, ERS was reduced according to the significant downregulation of 78 kDa glucose-regulated protein (GRP78), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF4) and activating transcription factor (ATF6). Our data shows that L/Zi provided functional and morphological preservation of photoreceptors against light damage, which is probably related to its mitigation of oxidative and endoplasmic reticulum stress.

Background/Aims: Our laboratory discovered a Kunming mouse with enormous electroretinogram (ERG) defects. Its auditory brainstem response (ABR) threshold was significantly elevated and closely resembled the features of Usher syndrome (USH). This study sought to cross these USH-like mice (named KM^ush/ush mice) with CBA/CaJ mice to establish recombinant inbred strains and identify their phenotypes and genotypes. Methods: KM^ush/ush mice were crossed with CBA/CaJ mice to establish inbred strains by sibling mating. ERG, ABR, ocular fundus morphology, histological examinations of the retina and inner ear, quantitative real-time polymerase chain reaction, western blotting, and exon sequencing were performed to assess the phenotypes and genotypes of the offspring strains. Results: The F1 hybrids from crossing KM^ush/ush and CBA/CaJ mice had normal ERG and ABR responses. The F2 offspring from intercrossing the F1 mice showed a segregation of the retinitis pigmentosa (RP) and hearing loss phenotypes. The CBA-1^ush/ush mice had an RP phenotype that was characterized by a vanished ERG waveform and loss of the outer nuclear layer. Their Pde6b gene had a nonsense mutation that resulted in the failure of protein production in western blotting. However, the ABR threshold of this strain of mice was normal. The CBA-2^ush/ush mice had normal retinal function and architecture. Their ABR threshold was increased, with a dramatic degeneration of the stereocilia bundles in the outer hair cells of the inner ear. Whole exome sequencing and exon sequencing revealed a deletion of one base pair in exon 31 of the Adgrv1 gene, which would result in the premature termination of protein encoding. The level of Adgrv1 mRNA was reduced in the CBA-2^ush/ush mice. The CBA-3^ush/ush mice had phenotypes of RP, elevated ABR threshold, and degeneration of the stereocilia bundles in the outer hair cells. They were closely associated with the nonsense mutations of Pde6b and Adgrv1, respectively. Conclusion: We isolated a mouse strain with hearing loss from inbred mice with retinal degeneration and established it as a recombinant inbred strain with a spontaneous mutation in Adgrv1, the human Usher syndrome 2C gene. The retinal degeneration was cause by a mutation in Pde6b, while the hearing loss was caused by a mutation in Adgrv1.

Branch retinal vein occlusion (BRVO) is a common retinal vascular disorder leading to visual impairment. Currently, the general strategies for BRVO are symptomatic therapies. Cardiovascular aspects are essential risk factors for BRVO. The traditional Chinese medicine hexuemingmu (HXMM), consisting of tanshinol and baicalin, dilates the vasculature and accelerates microcirculation. Therefore, the aim of this study was to determine the efficacy and possible mechanism of HXMM in a BRVO rat model established by laser photocoagulation. Successful BRVO rat models were treated with different doses of HXMM. Fundus photography and fluorescein fundus angiography (FFA) of the animals were applied. The retinal layers were measured by optical coherence tomography (OCT). Full-field electroretinography (ffERG) was applied to evaluate the retinal function. The ear vein flow velocity was measured via a microcirculation detector. The expression of the vascular endothelial growth factor (VEGF-α) was measured via western blotting and immunofluorescent staining. Our study found that retinal edema predominantly occurred in the inner nuclear layer (INL) and outer nuclear layer (ONL). The retinal edema of the treated groups was significantly relieved in the early stage of BRVO as visualized via OCT detection and HE staining. The amplitudes of the b wave and oscillatory potentials (OPs) waves of ffERG in the treated groups were increased compared with those of the control group at several detection points (3, 5, 7, 10, 14, and 21 d postocclusion). The expression of VEGF-α was reduced in the treated groups at an early stage of BRVO. Furthermore, the ear vein flow velocity of the HXMM treatment groups was faster than that of the control group. Thus, our study indicates that the traditional Chinese medicine HXMM could ameliorate retinal edema and rescue the retinal structure and function in BRVO models through promoting occluded vein recanalization, improving microcirculation, and regulating the expression of VEGF-α.