Search Results (51)

Stargardt’s disease (STGD1) is an autosomal recessive juvenile macular degeneration caused by mutations in the ABCA4 gene, impairing clearance of toxic retinoid byproducts in the retinal pigment epithelium (RPE). This leads to lipofuscin accumulation, oxidative stress, photoreceptor degeneration, and central vision loss. Over 1200 pathogenic/likely pathogenic ABCA4 variants highlight the genetic heterogeneity of STGD1, which manifests as progressive central vision loss, with phenotype influenced by deep intronic variants, modifier genes, and environmental factors like light exposure. ABCA4 variants also show variable penetrance and geographical prevalence. With no approved treatment, investigational therapies target different aspects of disease pathology. Small-molecule therapies target vitamin A dimerization (e.g., ALK-001), inhibit lipofuscin accumulation (e.g., soraprazan), or modulate the visual cycle (e.g., emixustat hydrochloride). Gene therapy trials explore ABCA4 supplementation including strategies like RNA exon editing (ACDN-01) and bioengineered ambient light-activated OPSIN. RORA gene therapy (Phase 2/3) addresses oxidative stress, inflammation, lipid metabolism, and complement system dysregulation. Trials like DRAGON (Phase 3, tinlarebant), STARLIGHT (phase 2, bioengineered OPSIN) show promise, but optimizing efficacy remains challenging. With the key problem of establishing genotype–phenotype correlations, the future of STGD1 therapy may rely on approaches targeting oxidative stress, lipid metabolism, inflammation, complement regulation, and genetic repair. Full article

Spiders are important predatory natural enemies in agricultural and forestry ecosystems, yet the role of vision in their predatory behavior remains unclear. In this study, we screened three opsin genes—corresponding to ultraviolet-sensitive and medium-to-long wavelength-sensitive opsins—from the transcriptome sequencing database of Pardosa astrigera. All three genes possess seven transmembrane topological structures and a lysine residue on the second transmembrane domain, which are typical characteristics of opsins. Using quantitative real-time PCR (RT-qPCR), we analyzed the expression patterns of these opsin genes in different tissues, developmental stages, and under the induction of light at three wavelengths. The results showed that all three opsin genes were significantly expressed in the cephalothorax and expressed across developmental stages with no significant differences. Under light induction, their relative expression first increased and then decreased in both male and female adult spiders. Subsequently, RNA interference (RNAi) was used to individually knock down each opsin gene, confirming their involvement in color vision. These results suggest that the three opsin genes are involved in spider vision, laying the foundation for further elucidating the role of vision in spider predation, and offering a new perspective for reducing the unintended killing of natural enemies by insect traps. Full article

Rhodopsin, a G-protein-coupled receptor (GPCR) comprising the protein opsin covalently linked to the chromophore 11-cis retinal, is pivotal in visual phototransduction. Mutations in the gene encoding rhodopsin (RHO) can cause opsin misfolding or reduce its stability, resulting in retinal degenerative disorders such as retinitis pigmentosa (RP). Current therapeutic strategies employing retinoid-based chaperones partially rescue the folding and trafficking of mutant rhodopsin, but are limited by inherent toxicity and instability due to photoinduced isomerization. In the present work, a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations was employed, leading to the identification of a novel non-retinoid opsin ligand that can potentially act as a pharmacological chaperone. Biological validation confirmed that the compound VS1 binds opsin effectively, representing a valuable starting point for structure-based optimization studies aimed at identifying new opsin stabilizers. Full article

During the early growth stages of fish larvae, there are significant challenges to their viability, so improving their visual environment is essential to promoting their growth and survival. Following the successful knockout of thyroid hormone receptor beta 2 (thrb2) using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, there was an increase in the expression of UV opsin (short-wave-sensitive 1, sws1), while the expression of other cone opsins was significantly decreased. Further analysis of the retinal structure demonstrated that the thrb2 knockout resulted in an increased lens thickness and a decreased thickness of the ganglion cell layer (GCL), outer plexiform layer (OPL), and outer nuclear layer (ONL) in the retina. The slowing down of swimming speed under light conditions in thrb2^−/− may be related to the decreased expression of phototransduction-related genes such as G protein-coupled receptor kinase 7a (grk7a), G protein-coupled receptor kinase 7b (grk7b), and phosphodiesterase 6c (pde6c). Notably, thrb2^−/− larvae exhibited a significant increase in the amount and proportion of first feeding, and their growth rate significantly exceeded that of wild-type controls during the week after feeding. This observation suggests that although the development of the retina may be somewhat affected, thrb2^−/− larvae show positive changes in feeding behaviour and growth rate, which may be related to their enhanced ability to adapt to their environment. These results provide novel insights into the function of the thrb2 gene in the visual system and behaviour and may have implications in areas such as fish farming and genetic improvement. 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

Opsin plays a regulatory role in phototaxis of Diaphorina citri, functioning as the initial station in the phototransduction cascade. Our study aimed to explore the D. citri phototransduction pathway to identify elicitors that may enhance D. citri phototaxis in the future. The RNAi technique was employed to inhibit LW-opsin gene expression, followed by RNA-Seq analysis to identify phototransduction genes. Finally, RT-qPCR was performed to validate whether genes in the phototransduction pathway were affected by the inhibition of LW-opsin expression. A total of 87 genes were identified within the transcriptome as involved in phototransduction based on KEGG functional annotation. Of these, 71 genes were identified as enriched in the phototransduction-fly pathway. These genes encode key proteins in this process, including Gqα, Gqβ, Gqγ, phospholipase C β (PLCβ), the cation channel transient receptor potential (TRP), and TRP-like (TRPL), among others. Moreover, the LOC103513214 (Gqβ) and LOC103518375 (ninaC) genes exhibited reduced expression when LW-opsin gene expression was suppressed. Our results provide a basis for further investigation of phototransduction in D. citri. Full article

The retina is crucial for converting light into neuronal signals for visual perception. Understanding the retina’s structure, function, and development is essential for vision research. It is known that the thyroid hormone (TH) receptor type beta 2 (TRβ2) is a key element in the regulation of cone differentiation in the retina, but other elements of TH signaling, such as transporters and enzyme deiodinases, have also been implicated in retinal cell development and survival. In the present study, we investigated the expression profile of genes involved in TH signaling and analyzed the impact of thyroidal status on retinal morphology, opsin expression, cell death/proliferation profile, as well as color preference behavior during the early retina development of zebrafish larvae. mRNA expression analysis on dissected whole eyes revealed that TH signaling elements gradually increase during eye development, with dio3b being the component that shows the most dramatic change. Mutations generated by CRISPR/CAS9 in the dio3b gene, but not in the thrb gene, modifies the structure of the retina. Disruption in TH level reduces the cell number of the ganglion cell layer, increases cell death, and modifies color preference, emphasizing the critical importance of precise TH regulation by its signaling elements for optimal retinal development and function. Full article

Mature and immature female swordfish show different gonadal expression patterns of melatonin synthesis-related and opsin genes, indicating that seasonality affects gonadal circadian genes, especially through opsin modulation. The high energy demands of reproduction may cause mature female swordfish to become more susceptible to environmental stressors/changes, potentially affecting their health post-reproduction. The modulation of melatonin and opsin expression may also influence swordfish biology, impacting basal metabolism and stress responses. This study aimed to investigate the hepatic expression patterns of genes involved in melatonin and opsins activity after the reproductive period, comparing mature and immature females. Liver samples of swordfish females, collected from the Central Adriatic Sea, were analyzed to evaluate the expression of a melatonin receptor (mel1b), acetylserotonin O-methyltransferase (asmt), opsins (sws, VA opsin and opsin4), and stress response (sod1, sod2 and hsp4b) genes, while histological analysis focused on hepatic melanomacrophages, melanomacrophage centers, and lipid content. The expression of all genes analyzed did not differ between mature and immature females except for sws, which was significantly downregulated in mature females. The overall health conditions of mature and immature females appeared comparable, as suggested by the histological analysis and the absence of significant differences in the expression of stress response genes. Although the study used a limited number of samples and lacked a comparison between the reproductive and non-reproductive periods, the preliminary results suggest that opsins may play a role in modulating physiological processes beyond reproduction. Full article

L-cone opsin expression by gene therapy is a promising treatment for blue cone monochromacy (BCM) caused by congenital lack of long- and middle-wavelength-sensitive (L/M) cone function. Eight patients with BCM and confirmed pathogenic variants at the OPN1LW/OPN1MW gene cluster participated. Optical coherence tomography (OCT), chromatic perimetry, chromatic microperimetry, chromatic visual acuity (VA), and chromaticity thresholds were performed with unmodified commercial equipment and/or methods available in the public domain. Adaptive optics scanning laser ophthalmoscope (AOSLO) imaging was performed in a subset of patients. Outer retinal changes were detectable by OCT with an age-related effect on the foveal disease stage. Rod and short-wavelength-sensitive (S) cone functions were relatively retained by perimetry, although likely impacted by age-related increases in the pre-retinal absorption of short-wavelength lights. The central macula showed a large loss of red sensitivity on dark-adapted microperimetry. Chromatic VAs with high-contrast red gratings on a blue background were not detectable. Color vision was severely deficient. AOSLO imaging showed reduced total cone density with majority of the population being non-waveguiding. This study developed and evaluated specialized outcomes that will be needed for the determination of efficacy and safety in human clinical trials. Dark-adapted microperimetry with a red stimulus sampling the central macula would be a key endpoint to evaluate the light sensitivity improvements. VA changes specific to L-opsin can be measured with red gratings on a bright blue background and should also be considered as outcome measures in future interventional trials. Full article

With a common aim of restoring physiological function of defective cells, optogenetics and targeted gene therapies have shown great clinical potential and novelty in the branch of personalized medicine and inherited retinal diseases (IRDs). The basis of optogenetics aims to bypass defective photoreceptors by introducing opsins with light-sensing capabilities. In contrast, targeted gene therapies, such as methods based on CRISPR-Cas9 and RNA interference with noncoding RNAs (i.e., microRNA, small interfering RNA, short hairpin RNA), consists of inducing normal gene or protein expression into affected cells. Having partially leveraged the challenges limiting their prompt introduction into the clinical practice (i.e., engineering, cell or tissue delivery capabilities), it is crucial to deepen the fields of knowledge applied to optogenetics and targeted gene therapy. The aim of this in-depth and novel literature review is to explain the fundamentals and applications of optogenetics and targeted gene therapies, while providing decision-making arguments for ophthalmologists. First, we review the biomolecular principles and engineering steps involved in optogenetics and the targeted gene therapies mentioned above by bringing a focus on the specific vectors and molecules for cell signalization. The importance of vector choice and engineering methods are discussed. Second, we summarize the ongoing clinical trials and most recent discoveries for optogenetics and targeted gene therapies for IRDs. Finally, we then discuss the limits and current challenges of each novel therapy. We aim to provide for the first time scientific-based explanations for clinicians to justify the specificity of each therapy for one disease, which can help improve clinical decision-making tasks. Full article

Opsins are a class of transmembrane proteins encoded by opsin genes, and they play a variety of functional roles. Short wavelength-sensitive opsin 2 (sws2), one of the five classes of visual opsin genes, mainly senses blue light. Previous research has indicated that sws2 is essential for melanocyte formation in fish; however, its specific role in skin color differentiation remains to be elucidated. Here, we identified the sws2 gene in a prized reef-dwelling fish, Plectropomus leopardus. The full-length P. leopardus sws2 gene encodes a protein consisting of 351 amino acids, and exhibits substantial homology with other fish species. The expression of the sws2 gene was widespread across P. leopardus tissues, with high expression in eye and skin tissues. Through immunohistochemistry and in situ hybridization analyses, we discovered that the sws2 gene was primarily localized in the rod and cone cells of the retina, and epidermal cells of the skin. Furthermore, dsRNA interference was used for sws2 gene knockdown in living P. leopardus to elucidate its function in skin color differentiation. Black-color-related genes, melanin contents, and tyrosinase activity in the skin significantly decreased after sws2 knockdown (p < 0.05), but red-color-related genes and carotenoid and lutein contents significantly increased (p < 0.05). Retinoic acid injection produced the opposite results. Our results suggested that the sws2 gene influences P. leopardus skin color regulation by affecting vitamin synthesis and melanin-related gene expression levels. This study establishes a foundation for elucidating the molecular mechanisms by which sws2 regulates melanocyte formation in fish skin. Full article

Phthorimaea absoluta (Meyrick) is an invasive pest that has caused damage to tomatoes and other crops in China since 2017. Pest control is mainly based on chemical methods that pose significant threats to food safety and environmental and ecological security. Light-induced control, a green prevention and control technology, has gained attention recently. However, current light-trapping technology is non-specific, attracting targeted pests alongside natural enemies and non-target organisms. In this study, we characterized the phototactic behavior of tomato leaf miners for the development a specific light-trapping technology for pest control. In situ hybridization revealed opsin expression throughout the body. Furthermore, we investigated the tropism of pests (wild T. absoluta, Toxoptera graminum, and Bemisia tabaci) and natural enemies (Nesidiocoris tenuis and Trichogramma pintoi) using a wavelength-lamp tropism experiment. We found that 365 ± 5 nm light could accurately trap wild P. absoluta without trapping natural enemies and other insects. Finally, we analyzed the phototactic behavior of the mutant strains LW2^(−/−) and BL^(−/−). LW2 and BL mutants showed significant differences in phototactic behavior. The LW2^(−/−) strain was attracted to light at 390 ± 5 nm and the BL^(−/−) strain was unresponsive to any light. Our findings will help to develop specific light-trapping technology for controlling tomato leaf miners, providing a basis for understanding pest population dynamics and protecting crops against natural enemies. Full article

The phototactic behavior of insects is commonly used to manage pest populations in practical production. However, this elusive behavior is not yet fully understood. Investigating whether the opsin genes play a crucial role in phototaxis is an intriguing topic. Vespinae (Hymenoptera: Vespidae) are a common group of social wasps that are closely associated with human activities. Efficiently controlling wasp populations while maintaining ecological balance is a pressing global challenge that still has to be resolved. This research aims to explore the phototactic behavior and key opsin genes associated with Vespinae. We found significant differences in the photophilic rates of Vespula germanica and Vespa analis under 14 different light conditions, indicating that their phototactic behavior is rhythmic. The results also showed that the two species exhibited varying photophilic rates under different wavelengths of light, suggesting that light wavelength significantly affects their phototactic behavior. Additionally, the opsin genes of the most aggressive hornet, Vespa basalis, have been sequenced. There are only two opsin genes, one for UV light and the other for blue light, and Vespa basalis lacks long-wavelength visual proteins. However, they exhibit peak phototaxis for long-wavelength light and instead have the lowest phototaxis for UV light. This suggests that the visual protein genes have a complex regulatory mechanism for phototactic behavior in Vespinae. Additionally, visual protein sequences have a high degree of homology among Hymenoptera. Despite the hypotheses put forward by some scholars regarding phototaxis, a clear and complete explanation of insect phototaxis is still lacking to date. Our findings provide a strong theoretical basis for further investigation of visual expression patterns and phototactic mechanisms in Vespinae. Full article

Blue light is the higher-energy region of the visible spectrum. Excessive exposure to blue light is known to induce oxidative stress and is harmful to the eyes. The stems of Dendrobium nobile Lindl. (Orchidaceae), named Jinchaishihu, have long been used in traditional Chinese medicine (TCM) for nourishing yin, clearing heat, and brightening the eyes. The polysaccharide is one of the major components in D. nobile. However, the effect on ocular cells remains unclear. This study aimed to investigate whether the polysaccharide from D. nobile can protect the eyes from blue light-induced injury. A crude (DN-P) and a partially purified polysaccharide (DN-PP) from D. nobile were evaluated for their protective effects on blue light-induced damage in ARPE-19 and 661W cells. The in vivo study investigated the electroretinographic response and the expression of phototransduction-related genes in the retinas of a Drosophila model. The results showed that DN-P and DN-PP could improve blue light-induced damage in ARPE-19 and 661W cells, including cell viability, antioxidant activity, reactive oxygen species (ROS)/superoxide production, and reverse opsin 3 protein expression in a concentration-dependent manner. The in vivo study indicated that DN-P could alleviate eye damage and reverse the expression of phototransduction-related genes, including ninaE, norpA, Gαq, Gβ76C, Gγ30A, TRP, and TRPL, in a dose-dependent manner in blue light-exposed Drosophila. In conclusion, this is the first report demonstrating that D. nobile polysaccharide pretreatment can protect retinal cells and retinal photoreceptors from blue light-induced damage. These results provide supporting evidence for the beneficial potential of D. nobile in preventing blue light-induced eye damage and improving eyesight. Full article

It is unclear whether normal human skin tissue or abnormal scarring are photoreceptive. Therefore, this study investigated photosensitivity in normal skin tissue and hypertrophic scars. The expression of opsins, which are photoreceptor proteins, in normal dermal fibroblasts (NDFs) and hypertrophic scar fibroblasts (HSFs) was examined. After exposure to blue light (BL), changes in the expression levels of αSMA and clock-related genes, specifically PER2 and BMAL1, were examined in both fibroblast types. Opsins were expressed in both fibroblast types, with OPN3 exhibiting the highest expression levels. After peripheral circadian rhythm disruption, BL induced rhythm formation in NDFs. In contrast, although HSFs showed changes in clock-related gene expression levels, no distinct rhythm formation was observed. The expression level of αSMA was significantly higher in HSFs and decreased to the same level as that in NDFs upon BL exposure. When OPN3 knocked-down HSFs were exposed to BL, the reduction in αSMA expression was inhibited. This study showed that BL exposure directly triggers peripheral circadian synchronization in NDFs but not in HSFs. OPN3-mediated BL exposure inhibited HSFs. Although the current results did not elucidate the relationship between peripheral circadian rhythms and hypertrophic scars, they show that BL can be applied for the prevention and treatment of hypertrophic scars and keloids. Full article