Search Results (70)

The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood–retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles’ (EVs’) signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood–retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies. Full article

Pollinating fig wasps (Agaonidae) engage in an obligate mutualism with Ficus species, which is mediated by host-specific chemical cues. However, the role of visual perception in host recognition remains poorly understood, particularly because of a lack of structural studies of their compound eyes. We investigated the ocular morphology of female Ceratosolen gravelyi (exclusive pollinator of F. semicordata) using scanning/transmission electron microscopy. The oval apposition eyes contain 228–263 ommatidia, which are asymmetrically distributed between the left and right eyes. Each ommatidium comprises a biconvex corneal lens overlying a tetrapartite eucone crystalline cone; proximal cone cells reveal an interlaced labyrinth. Pigment cells encapsulate each ommatidium, and numerous pigment granules and mitochondria are present in both pigment and retinular cells. Nine retinular cells comprise a unit, with eight photoreceptors (R1–R8) forming the rhabdom from the cone base to the basal matrix; a ninth cell replaces R8 in the apical third of the rhabdom. Optical metrics, including F-number (1.1°), acceptance angle (10.0°), and ommatidial sensitivity (0.26 µm²/sr), indicate diurnal activity in bright environments. These adaptations suggest that their eyes are critical for processing visual cues during host interactions, which advances our understanding of multimodal sensory integration in fig–wasp mutualism. Full article

The scope of this study was to evaluate the response of Ce-doped gadolinium aluminum gallium garnet (GAGG:Ce) crystalline scintillator under medical X-ray irradiation for medical imaging applications. A 10 × 10 × 10 mm³ crystal was irradiated at X-ray tube voltages ranging from 50 kVp to 150 kVp. The crystal’s compatibility with several commercially available optical photon detectors was evaluated using the spectral matching factor (SMF) along with the absolute efficiency (AE) and the effective efficiency (EE). In addition, the energy-absorption efficiency (EAE), the quantum-detection efficiency (QDE) as well as the zero-frequency detective quantum detection efficiency DQE(0) were determined. The crystal demonstrated satisfactory AE values as high as 26.3 E.U. (where 1 E.U. = 1 μW∙m⁻²/(mR∙s⁻¹)) at 150 kVp, similar, or in some cases, even superior to other cerium-doped scintillator materials. It also exhibits adequate DQE(0) performance ranging from 0.99 to 0.95 across all the examined X-ray tube voltages. Moreover, it showed high spectral compatibility with commonly used photoreceptors in modern day such as complementary metal–oxide–semiconductors (CMOS) and charge-coupled-devices (CCD) with SMF values of 0.95 for CCD with broadband anti-reflection coating and 0.99 for hybrid CMOS blue. The aforementioned properties of this scintillator material were indicative of its superior efficiency in the examined medical energy range, compared to other commonly used scintillators. Full article

Retinal homeostasis and degeneration are significant contributors to global vision loss, with retinal health primarily assessed by the count and function of photoreceptor cells, the most abundant cells in the retina. Genomic studies have identified topoisomerase II beta (Top2b), an enzyme that untangles DNA supercoils to facilitate gene expression, as a critical transcriptional regulator for retinal health. This review aims to uncover and categorize genes linked to Top2b that are dynamically expressed during retinal degeneration, revealing shared and overlooked regulatory pathways. RNA sequencing data from wild-type and Top2b knockout mice revealed thousands of differentially expressed genes regulated by Top2b. By cross-referencing these genes with retinal degeneration datasets, including RetNet and the Gene Ontology Browser, we identified 44 Top2b-linked genes associated with retinal degeneration. These genes were grouped into fourteen functional categories: ciliary function and trafficking, metabolism, synaptic transmission, transcription factors and regulation, visual cycle, retinoids, and more. Key genes such as Bbs7, Ubb, Rbp4, Cetn2, Pik3r1, and Crx were explored, and their critical pathways for retinal health were outlined. This comprehensive catalog of 44 Top2b-linked retinal homeostatic genes will serve as a valuable resource for researchers. It provides new insights into the regulatory mechanisms underlying retinal homeostasis, setting the framework for the development of targeted therapeutic approaches and early intervention strategies for preventing photoreceptor loss. Full article

Background/Objectives: Identifying effective and safe treatment options for non-infectious uveitis remains challenging due to chronic and relapsing ocular inflammation. Previous studies have shown that artesunate (ART) plays an immunosuppressive role in several classic autoimmune diseases, including uveitis. However, its impact on the plasma metabolic profile of recurrent autoimmune uveitis remains unclear. This study aims to explore the effect of ART on the plasma metabolic features of recurrent experimental autoimmune uveitis (EAU) in a Lewis rat. Methods: Rats were clinically and pathologically evaluated for the development of recurrent EAU induced by inter-photoreceptor retinoid-binding protein (IRBP) R16 peptide-specific T-cells (tEAU). The disruptive effects of ART on tEAU were investigated to evaluate the potential role of rat recurrent EAU. Differentially expressed metabolites were identified in the plasma of rats by untargeted metabolomics analysis after ART treatment. The differential metabolites were applied to subsequent pathway analysis and biomarker analysis by MetaboAnalyst. Results: ART can significantly alleviate the severity of clinical signs and pathological injuries of eyeballs with tEAU. Both non-supervised principal component analysis and orthogonal partial least-squares discriminant analysis showed 84 differential metabolites enriched in 16 metabolic pathways in the tEAU group compared with heathy controls and 51 differential metabolites enriched in 17 metabolic pathways, including arginine and proline metabolism, alanine metabolism, and aminoacyl-tRNA biosynthesis, in the ART-treated group compared with the tEAU group. Particularly, upregulated L-alanine levels in both alanine metabolism and aminoacyl-tRNA biosynthesis were associated with T-cell activation, while elevated spermidine and N-acetyl putrescine levels in arginine and proline metabolism related to T-cell differentiation proved to be valuable biomarkers for ART treatment. Conclusions: Our study demonstrates that ART treatment can alleviate recurrent uveitis by altering the plasma metabolic characteristics associated with T-cell activation and differentiation, which might provide novel insights for potential therapeutic treatments. Full article

Retinal degenerations, such as age-related macular degeneration and retinitis pigmentosa, present significant challenges due to genetic heterogeneity, limited therapeutic options, and the progressive loss of photoreceptors in advanced stages. These challenges are compounded by difficulties in precisely targeting residual retinal neurons and ensuring the sustained efficacy of interventions. Optogenetics offers a novel approach to vision restoration by inducing light sensitivity in residual retinal neurons through gene delivery of light-sensitive opsins. This review traces the evolution of opsins in optogenetic therapies, highlighting advancements from early research on channelrhodopsin-2 (ChR2) to engineered variants addressing key limitations. Red-shifted opsins, including ReaChR and ChrimsonR, reduced phototoxicity by enabling activation under longer wavelengths, while Chronos introduced superior temporal kinetics for dynamic visual tracking. Further innovations, such as Multi-Characteristic Opsin 1 (MCO1), optimized opsin performance under ambient light, bridging the gap to real-world applications. Key milestones include the first partial vision restoration in a human patient using ChrimsonR with light-amplifying goggles and ongoing clinical trials exploring the efficacy of opsin-based therapies for advanced retinal degeneration. While significant progress has been made, challenges remain in achieving sufficient light sensitivity for functional vision under normal ambient lighting conditions in a manner that is both effective and safe, eliminating the need for external light-enhancing devices. As research progresses, optogenetic therapies are positioned to redefine the management of retinal degenerative diseases, offering new hope for millions affected by vision loss. Full article

(1) Background: At present, the bio-inspired visual neural models have made significant achievements in detecting the motion direction of the translating object. Variable contrast in the figure-ground and environmental noise interference, however, have a strong influence on the existing model. The responses of the lobula plate tangential cell (LPTC) neurons of Drosophila are robust and stable in the face of variable contrast in the figure-ground and environmental noise interference, which provides an excellent paradigm for addressing these challenges. (2) Methods: To resolve these challenges, we propose a bio-inspired visual neural model, which consists of four stages. Firstly, the photoreceptors (R1–R6) are utilized to perceive the change in luminance. Secondly, the change in luminance is divided into parallel ON and OFF pathways based on the lamina monopolar cell (LMC), and the spatial denoising and the spatio-temporal lateral inhibition (LI) mechanisms can suppress environmental noise and improve motion boundaries, respectively. Thirdly, the non-linear instantaneous feedback mechanism in divisive contrast normalization is adopted to reduce local contrast sensitivity; further, the parallel ON and OFF contrast pathways are activated. Finally, the parallel motion and contrast pathways converge on the LPTC in the lobula complex. (3) Results: By comparing numerous experimental simulations with state-of-the-art (SotA) bio-inspired models, we can draw four conclusions. Firstly, the effectiveness of the contrast neural computation and the spatial denoising mechanism is verified by the ablation study. Secondly, this model can robustly detect the motion direction of the translating object against variable contrast in the figure-ground and environmental noise interference. Specifically, the average detection success rate of the proposed bio-inspired model under the pure and real-world complex noise datasets was increased by 5.38% and 5.30%. Thirdly, this model can effectively reduce the fluctuation in this model response against variable contrast in the figure-ground and environmental noise interference, which shows the stability of this model; specifically, the average inter-quartile range of the coefficient of variation in the proposed bio-inspired model under the pure and real-world complex noise datasets was reduced by 38.77% and 47.84%, respectively. The average decline ratio of the sum of the coefficient of variation in the proposed bio-inspired model under the pure and real-world complex noise datasets was 57.03% and 67.47%, respectively. Finally, the robustness and stability of this model are further verified by comparing other early visual pre-processing mechanisms and engineering denoising methods. (4) Conclusions: This model can robustly and steadily detect the motion direction of the translating object under variable contrast in the figure-ground and environmental noise interference. Full article

Objectives: This study aimed to assess the role of macular pigment optical density (MPOD) in patients with a full-thickness macular hole (FTMH) compared to healthy controls, evaluating postoperative changes in MPOD and exploring potential correlations with visual outcomes. Methods: This prospective, cross-sectional, comparative study included 16 eyes from FTMH patients who achieved anatomical hole closure following pars plana vitrectomy with the inverted ILM flap technique. Each eye underwent a comprehensive ophthalmologic examination, including BCVA and intraocular pressure measurements, anterior segment evaluation, fundus examination, and macular assessment with Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT, Spectralis, Heidelberg Engineering Inc., Heidelberg, Germany). Macular pigment optical density (MPOD) was measured using one-wavelength reflectometry (Visucam 200, Zeiss Meditec, Jena, Germany). These evaluations were conducted preoperatively and at 1, 3, and 6 months postoperatively to assess changes over time and correlate MPOD with visual outcomes. Results: Significant baseline differences were observed between FTMH patients and controls for BCVA, mean MPOD, maximum MPOD, and MPOD volume (p < 0.05). Postoperative BCVA improved significantly (p = 0.0011), with a notable increase in MPOD volume at 6 months (p = 0.01). A positive correlation was found between BCVA improvement and MPOD volume increase (r = 0.739; p = 0.002). Conclusions: In conclusion, MPOD measurement may serve as a valuable addition to the follow-up of FTMH surgery, providing insights into photoreceptor function and macular metabolic activity, potentially correlating with visual recovery. Further longitudinal studies are needed to clarify its relationship with clinical variables, such as metamorphopsia and OCT microstructural findings. Full article

Background: This study aimed to analyze the potential pathogenic connection between metabolic factors, photoreceptor cell rearrangements, retinal microvascular perfusion, and functional parameters through multifocal electroretinography (mfERG) in type 1 diabetes mellitus (DM1). Methods: This prospective observational cohort study enrolled DM1 patients (40.5 ± 9.1 years) with mild nonproliferative diabetic retinopathy followed for 4 years. Patients were subjected to multimodal imaging, which included color fundus photography, optical coherence tomography (OCT), OCT angiography, adaptive optics (AO), and mfERG. OCTA slabs were analyzed using ImageJ software (software version 2.3.0/1.53f) to calculate perfusion density (PD) at both superficial (SCP) and deep (DCP) capillary plexuses, as well as flow deficit percentage (FD%) at the choriocapillaris (CC). To calculate cone metrics on AO at the parafovea, including cone density (CD), linear dispersion index (LDi), and heterogeneity packing index (Hpi%) in the parafovea, the images were post-processed using a MATLAB algorithm. The mfERG P1 implicit time (IT) and N1-P1 response amplitude density (RAD) from R1 (foveal area), R2 (parafoveal area), and the unified rings R1 + R2 were evaluated. Results: A total of 22 patients (22 eyes) were enrolled. No significant differences were noted in central mfERG amplitude and implicit time-averaged values (p > 0.05, all). The main factor influencing R1 IT was HbA1c, while R1 RAD was affected by Hpi and CC FD%. R1 + R2 IT was influenced by Hpi, LDi (p > 0.001, all), and modifications in the perfusion density in the SCP (p < 0.001) and DCP (p = 0.03) at the parafovea. In contrast, R1 + R2 RAD were associated with HbA1c (p = 0.02) and Hpi (p < 0.001). Conclusions: Microvascular changes and glucometabolic factors are key elements influencing the long-term morphofunctional alterations at the photoreceptor level in DM1. Full article

Background/Objectives: Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) leading to the progressive and irreversible loss of visual function. Characteristics of GA include atrophic lesions resulting from the loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. During GA progression, atrophic lesions typically advance from the macular periphery to the center, affecting foveal light sensitivity and visual acuity. This study analyzed changes in light sensitivity and visual acuity during the natural course of GA progression using the topographic analysis of structural and functional changes based on Early Treatment Diabetic Retinopathy Study (ETDRS) charts, multimodal imaging, and microperimetry assessment. Methods: Medical chart data of GA patients between 2014 and 2022 from the Internationale Innovative Ophthalmochirurgie GbR (I.I.O.) research center (Düsseldorf, Germany) were retrospectively analyzed. All patient eyes fulfilling the phase 3 OAKS study inclusion criteria were included and followed up for 60 months. The imputation of missing measurements and dropouts was performed by linear mixed models. Results: A total of 20 GA eyes from 13 GA patients were included in the study. At the index, 53.8% of patients had bilateral GA, with 70.0% of the eyes showing multifocal GA and 30.0% subfoveal encroachment (SFE). A total of 35.0% of the eyes had 2–5, and 15.0% over 20, areas of atrophy. Over time, the GA lesion size increased from 6.4 mm² to 11.8 mm² (1.08 mm²/year). After an average observation time of 2.9 years, 78.6% of the initially unaffected study eyes developed SFE. The percentage of study eyes without visual impairment decreased from 55.0% to 30.0%, with mean normal-luminance best-corrected visual acuity (NL-BCVA) reducing from 63.7 to 55.7 ETDRS letters. The share of absolute scotoma points in microperimetry assessment increased from 15.7% to 43.5% while overall average macular sensitivity declined from 15.7 dB to 7.4 dB. Conclusions: The substantial deterioration of macular outcomes and visual function was comprehensively detected. The results were a documentation of structural and functional aspects of the natural progression of GA for a 60-month follow-up, providing a typical outline for AMD patients with GA. Full article

We generated a novel Cre mouse strain for cell-specific deletion of floxed genes in ribbon synapse-forming retinal neurons. Previous studies have shown that the RIBEYE promotor targets the expression of recombinant proteins such as fluorescently tagged RIBEYE to photoreceptors and retinal bipolar cells and generates fluorescent synaptic ribbons in situ in these neurons. Here, we used the same promotor to generate a novel transgenic mouse strain in which the RIBEYE promotor controls the expression of a Cre-ER(T2) recombinase (RIBEYE-Cre). To visualize Cre expression, the RIBEYE-Cre animals were crossed with ROSA26 tau-GFP (R26-τGFP) reporter mice. In the resulting RIBEYE-Cre/R26 τGFP animals, Cre-mediated removal of a transcriptional STOP cassette results in the expression of green fluorescent tau protein (tau-GFP) that binds to cellular microtubules. We detected robust tau-GFP expression in retinal bipolar cells. Surprisingly, we did not find fluorescent tau-GFP expression in mouse photoreceptors. The lack of tau-GFP reporter protein in these cells could be based on the previously reported absence of tau protein in mouse photoreceptors which could lead to the degradation of the recombinant tau protein. Consistent with this, we detected Cre and tau-GFP mRNA in mouse photoreceptor slices by RT-PCR. The transgenic RIBEYE-Cre mouse strain provides a new tool to study the deletion of floxed genes in ribbon synapse-forming neurons of the retina and will also allow for analyzing gene deletions that are lethal if globally deleted in neurons. Full article

Retinoblastoma represents the most prevalent malignant neoplasm affecting the eyes in childhood. The clear-cut origin of retinoblastoma has not yet been determined; however, based on experiments, it has been suggested that RB1 loss in cone photoreceptors causes retinoblastoma. Pituitary adenylate-cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide which has been shown to be affected in certain tumorous transformations, such as breast, lung, kidney, pancreatic, colon, and endocrine cancers. This study aimed to investigate potential changes in both PACAP38 and PAC1 receptor (PAC1R) expression in human retinoblastoma and the effect of PACAP38 administration on the survival of a human retinoblastoma cell line (Y-79). We analyzed human enucleation specimens removed because of retinoblastoma for PACAP38 and PAC1R immunostaining and the effect of PACAP38 on the survival of the Y-79 cell line. We described for the first time that human retinoblastoma cells from patients showed only perinuclear, dot-like immunopositivity for both PACAP38 and PAC1R, irrespective of laterality, genetic background, or histopathological features. Nanomolar (100 nM and 500 nM) PACAP38 concentrations had no effect on the viability of Y-79 cells, while micromolar (2 µM and 6 µM) PACAP38 significantly decreased tumor cell viability. These findings, along with general observations from animal studies showing that PACAP38 has strong anti-apoptotic, anti-inflammatory, and antioxidant effects on ocular tissues, together suggest that PACAP38 and its analogs are promising candidates in retinoblastoma therapy. Full article

Temperature plays an essential role in a plant’s life. The current investigation reveals that photoreceptors, whose activity is affected by the geomagnetic field, are a critical element of its perception. This knowledge suggests that plants’ responses to temperature could shift in different geomagnetic conditions. To test this hypothesis, we studied the change in the growth response of the peat moss Sphagnum riparium to temperature with a gradual increase in the geomagnetic K_p index. Growth data for this species were collected from Karelian mires by detailed monitoring over eight full growing seasons. The growth of 209,490 shoots was measured and 1439 growth rates were obtained for this period. The analysis showed a strong positive dependence of sphagnum growth on temperature (r = 0.58; n = 1439; P = 1.7 × 10⁻¹¹⁹), which is strongest in the K_p range from 0.87 to 1.61 (r = 0.65; n = 464; P = 4.5 × 10⁻⁵⁸). This K_p interval is clearer after removing the seasonal contributions from the growth rate and temperature and is preserved when diurnal temperature is used. Our results are consistent with the hypothesis and show the unknown contribution of the geomagnetic field to the temperature responses of plants. Full article

The manual segmentation of retinal layers from OCT scan images is time-consuming and costly. The deep learning approach has potential for the automatic delineation of retinal layers to significantly reduce the burden of human graders. In this study, we compared deep learning model (DLM) segmentation with manual correction (DLM-MC) to conventional manual grading (MG) for the measurements of the photoreceptor ellipsoid zone (EZ) area and outer segment (OS) volume in retinitis pigmentosa (RP) to assess whether DLM-MC can be a new gold standard for retinal layer segmentation and for the measurement of retinal layer metrics. Ninety-six high-speed 9 mm 31-line volume scans obtained from 48 patients with RPGR-associated XLRP were selected based on the following criteria: the presence of an EZ band within the scan limit and a detectable EZ in at least three B-scans in a volume scan. All the B-scan images in each volume scan were manually segmented for the EZ and proximal retinal pigment epithelium (pRPE) by two experienced human graders to serve as the ground truth for comparison. The test volume scans were also segmented by a DLM and then manually corrected for EZ and pRPE by the same two graders to obtain DLM-MC segmentation. The EZ area and OS volume were determined by interpolating the discrete two-dimensional B-scan EZ-pRPE layer over the scan area. Dice similarity, Bland–Altman analysis, correlation, and linear regression analyses were conducted to assess the agreement between DLM-MC and MG for the EZ area and OS volume measurements. For the EZ area, the overall mean dice score (SD) between DLM-MC and MG was 0.8524 (0.0821), which was comparable to 0.8417 (0.1111) between two MGs. For the EZ area > 1 mm², the average dice score increased to 0.8799 (0.0614). When comparing DLM-MC to MG, the Bland–Altman plots revealed a mean difference (SE) of 0.0132 (0.0953) mm² and a coefficient of repeatability (CoR) of 1.8303 mm² for the EZ area and a mean difference (SE) of 0.0080 (0.0020) mm³ and a CoR of 0.0381 mm³ for the OS volume. The correlation coefficients (95% CI) were 0.9928 (0.9892–0.9952) and 0.9938 (0.9906–0.9958) for the EZ area and OS volume, respectively. The linear regression slopes (95% CI) were 0.9598 (0.9399–0.9797) and 1.0104 (0.9909–1.0298), respectively. The results from this study suggest that the manual correction of deep learning model segmentation can generate EZ area and OS volume measurements in excellent agreement with those of conventional manual grading in RP. Because DLM-MC is more efficient for retinal layer segmentation from OCT scan images, it has the potential to reduce the burden of human graders in obtaining quantitative measurements of biomarkers for assessing disease progression and treatment outcomes in RP. Full article

The cGMP-phosphodiesterase 6 beta subunit (PDE6B) is an essential component in the phototransduction pathway for light responses in photoreceptor cells. PDE6B gene mutations cause the death of rod photoreceptors, named as hereditary retinitis pigmentosa (RP) in humans and retinal degeneration (RD) in rodents. Here, we report a new RD model, identified from a phenotypic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice, which displays retinal degeneration caused by a point mutation in the Pde6b gene that results in PDE6B-T592I mutant protein. The homozygous mutant mice show an extensive loss of rod photoreceptors at the age of 3 weeks; unexpectedly, the loss of rod photoreceptors can be partly rescued by dark rearing. Thus, this RD mutant model displays a light-dependent loss of rod photoreceptors. Both western blot and immunostaining results show very low level of mutant PDE6B-T592I protein in the retina. Structure modeling suggests that the T592I mutation probably affects the function and stability of PDE6B protein by changing intramolecular interactions. We further demonstrate that the expression of wild-type PDE6B delivered by subretinally injected adeno-associated virus (rAAV) prevents photoreceptor cell death in this RD model in vivo. The PDE6B-T592I mutant is, therefore, a valuable RD model for evaluating rAAV-mediated treatment and for investigating the molecular mechanism of light-dependent rod photoreceptor cell death that is related to impaired PDE6B function. Full article