Photoreceptor cell death, primarily through apoptosis, related to retinal disorders like retinitis pigmentosa (RP), would result in vision loss. The pathological processes and crucial mutant conditions preceding photoreceptor cell demise are not well understood. This study aims to conduct an in-depth examination of early-stage changes in the widely utilized Pde6b^rd1/rd1 (rd1) mouse model, which has Pde6b gene mutations representing autosomal recessive RP disorder. We investigated the morphology and ultrastructure of retinal cells, including second-order neurons, during the initial phase of disease progression. Our findings revealed that mitochondrial alterations in rod photoreceptors were present as a predeath mutant state as early as postnatal day 3 (P3). The bipolar and horizontal cells from the rd1 mouse retina exhibited significant morphological changes in response to loss of photoreceptor cells, indicating that second-order neurons rely on these cells for their structures. Subsequent oral administration of idebenone, a mitochondria-protective agent, enhanced retinal function and promoted both photoreceptor cell survival and inner retinal second-order synaptogenesis in rd1 mice at P14. Our findings offer a mechanistic framework, suggesting that mitochondrial damage acts as an early driver for photoreceptor cell death in retinal degeneration.

Objective Our research was performed in order to explore the effects of molecular hydrogen (H₂), a novelly-established antioxidant, on the retinal degeneration in rd1 mice, an animal model of inherited retinitis pigmentosa (RP).Methods The rd1 mice were divided randomly into control and H₂ intervention groups. Mice from other groups received H₂ intervention in three modes, two modes of the hydrogen gas (HG) and one model of hydrogen-rich saline (HRS). At 14 days post born (P14) and P21, various indicators were detected in all mice, including eletroretinogram (ERG), fundus phography, optical coherence tomography (OCT), and retinal immunotaining of microglia cells’ marker, Iba1.Results The ERG amplitude in mice from the control and H₂ intervention groups showed no statistical differences (p > 0.05). At P14 and P21, no significant difference in the distance from the retinal pigment epithelium to the outer plexiform layer on OCT from mice of the above two groups was found (p > 0.05). The thickness of the outer nuclear layer (ONL) in mice at P14 and P21 showed no statistical differences between the control group and the H₂ intervention group (p > 0.05). In the aspect of the number of Iba1-positive cells, we did not found any significant differences between the two groups (p > 0.05).Conclusion Different forms of H₂ intervention (hydrogen-rich saline and hydrogen gas) had no obvious effects on the course of retinal degeneration in rd1 mice. The specific mechanism of photoreceptor degeneration in the hereditary RP mouse model may be different, requiring different medical interventions.

Severe retinopathy of prematurity (ROP) with extremely unfavorable prognosis among infants can do great damage to individuals and bring tremendous social-economic burden. The purpose of this study is to describe the demographic and ocular characteristics of infants who presented with stage 5 ROP in order to identify reasons why they have become blind, and to identify contributing factors in order to focus great attention on the current ROP program and to inspire more effort in ROP screening in middle income countries. A retrospective review of consecutive infants with stage 5 ROP from December 2010 to December 2016 in Department of Ophthalmology, Xijing Hospital. Various parameters retrieved included birthweight, gestational age, age at initial examination, postmenstrual age, screening details, check-up details and reasons for consultation. Ocular findings were recorded and also detected by ultrasonography. A retrospective review of 20 consecutive infants with stage 5 ROP are included. Mean birthweight was1712.3 ± 512.97 g and mean gestational age at birth was 32.1 ± 2.21 weeks. Median age at first consultancy was 9.7 month. Median postmenstrual age first consultancy was 52 weeks. All infants were never screened for ROP before they came to the referral center. Of twenty stage 5 ROP infants, 13 cases presented with bilateral stage 5 features. Of the 40 eyes of 20 infants, 33 eyes were diagnosed as stage 5. Leukocoric pupil, closed funnel configuration of retinal detachment (RD), posterior synechia, extraretinal fibrovascular proliferation and retinal folds were the most significant indicators of bad prognosis. Ten eyes appeared no fixation to light, while 30 eyes exhibited following to light or following to toys. Our study shows that in relatively less-developed regions of China, more needs to be done to spread awareness about the disease among pediatricians, neonatologists and ophthalmologists as well as parents of premature infants. Thus, a comprehensive control system which is a whole network of propaganda, screening, treatment and follow-up are encouraged especially in less developed areas in China as well as worldwide.

AIM: To demonstrate the feasibility of mesenchymal stem cell (MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxia-inducible factor-1α small interfering RNA (HIF-1α siRNA) between MSCs and retinal pigment epithelial cells (RPE) under hypoxia environment. METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α siRNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) through the water-in-oil-in-water (w/o/w) multiple emulsion technique. The effect of PLGA-NPs uptake on the expression of HIF-1α mRNA was tested in RPE cells by real-time quantitative polymerase chain reaction (qPCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α siRNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using qPCR at the time points 24h, 3d, and 7d. RESULTS: The average diameter of PLGA-NPs loaded with HIF siRNA was 314.1 nm and the zeta potential was -0.36 mV. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α siRNA can effectively reduce the expression of HIF-1α mRNA up to 7d in RPE (0.63±0.05 at 7d, P<0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation (2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis (14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%; F=0.70, P=0.53) and migration (124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSC-loaded HIF-1α siRNA PLGA-NPs and other groups. The inhibition of PLGA on the HIF-1α mRNA expression in RPE cells could continue until the 7th day, the level of HIF-1α mRNA was lower than that of other groups (F=171.98, P<0.001). CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α siRNA carried by MSCs is found to be beneficial temporally for HIF-1α mRNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α siRNA nanoparticles is a potential method for therapy against choroidal neovascularization.

To investigate the sensitivity and potential application of steady-state flash visual evoked potentials (SSFVEP) in assessing the visual function of fundus diseases with vitreous hemorrhage. 18 patients diagnosed with monocular vitreous hemorrhages in the fundus were examined the flash visual evoked potentials (FVEP) and SSFVEP in both eyes. The difference in the P2-wave amplitude of FVEP and the average amplitude of SSFVEP waveform between the diseased eyes and those without vitreous hemorrhage were statistically compared. There was no significant difference in the waveform of FVEP between both eyes. The amplitude of P2-wave from FVEP of the diseased eye was slightly lower than that without vitreous hemorrhage. However, the difference was not statistically significant (P = 0.111). The waveform of SSFVEP in the eye without vitreous hemorrhage showed a towering shape, while that of the diseased eye was flat. The average amplitude of SSFVEP in the diseased eye was statistically lower than that without vitreous hemorrhage (P = 0.036). The difference ratio of SSFVEP amplitude between both eyes was significantly greater than that of FVEP amplitude (P = 0.028). In some fundus diseases with vitreous hemorrhage, SSFVEP had a higher sensitivity than FVEP, providing a novel potential application for visual function assessment.

To develop an algorithm using deep learning methods to calculate the volume of intraretinal and subretinal fluid in optical coherence tomography (OCT) images for assessing diabetic macular edema (DME) patients’ condition changes. Cross-sectional study. Treatment-naive patients diagnosed with DME recruited from April 2020 to November 2021. The deep learning network, which was built for autonomous segmentation utilizing an encoder-decoder network based on the U-Net architecture, was used to calculate the volume of intraretinal fluid (IRF) and subretinal fluid (SRF). The alterations of retinal vessel density and thickness, and the correlation between best-corrected visual acuity (BCVA) and OCT parameters were analyzed. 2,955 OCT images of fourteen eyes from DME patients with IRF and SRF who received anti-vascular endothelial growth factor (VEGF) agents were obtained. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the algorithm was 0.993 for IRF and 0.998 for SRF. The volumes of IRF and SRF were significantly decreased from 1.93 ± 0.58 /1.14 ± 0.25 mm³ (baseline) to 0.26 ± 0.13 /0.26 ± 0.18 mm³ (post-injection), respectively (p = 0.0170 for IRF, and p = 0.0004 for SRF). The Spearman correlation demonstrated that the reduction of IRF volume was negatively correlated with age (coefficient = −0.698, p = 0.006). We developed a deep learning assisted fluid volume calculation algorithm with high sensitivity and specificity for assessing the volume of IRF and SRF in DME patients. Key words: deep learning; diabetic macular edema; optical coherence tomography.