UWAFA-GAN: Ultra-Wide-Angle Fluorescein Angiography Transformation via Multi-scale Generation and Registration Enhancement.

Fundus photography, in combination with the ultra-wide-angle fundus (UWF) techniques, becomes an indispensable diagnostic tool in clinical settings by offering a more comprehensive view of the retina. Nonetheless, UWF fluorescein angiography (UWF-FA) necessitates the administration of a fluorescent dye via injection into the patient's hand or elbow unlike UWF scanning laser ophthalmoscopy (UWF-SLO). To mitigate potential adverse effects associated with injections, researchers have proposed the development of cross-modality medical image generation algorithms capable of converting UWF-SLO images into their UWF-FA counterparts. Current image generation techniques applied to fundus photography encounter difficulties in producing high-resolution retinal images, particularly in capturing minute vascular lesions. To address these issues, we introduce a novel conditional generative adversarial network (UWAFA-GAN) to synthesize UWF-FA from UWF-SLO. This approach employs multi-scale generators and an attention transmit module to efficiently extract both global structures and local lesions. Additionally, to counteract the image blurriness issue that arises from training with misaligned data, a registration module is integrated within this framework. Our method performs non-trivially on inception scores and details generation. Clinical user studies further indicate that the UWF-FA images generated by UWAFA-GAN are clinically comparable to authentic images in terms of diagnostic reliability. Empirical evaluations on our proprietary UWF image datasets elucidate that UWAFA-GAN outperforms extant methodologies. The code is accessible at https://github.com/Tinysqua/UWAFA-GAN.

An anti-GD2 aptamer-based bifunctional spherical nucleic acid nanoplatform for synergistic therapy targeting MDM2 for retinoblastoma.

Retinoblastoma (RB) is a type of pediatric solid tumor in the fundus. The lack of precision therapies combined with the difficulty of delivering small interfering RNA (siRNA) into the eyes means that there is currently no nucleic acid-based therapy for RB in clinical practice. Here, we reported on anti-GD2 and glutathione-responsive spherical nucleic acids (SNAs), loaded with siRNA and the inhibitor NVP-CGM097, which jointly blocked the oncogenic factor n in RB cells (Y79 and WERI-RB-1). The SNAs were formed through the self-assembly of bifunctional cholesterol amphiphiles containing aptamers that specifically targeted GD2-positive RB cells, allowing for the formation of an SNA with a dense DNA shell. The aptamer/siRNA component functioned both as a carrier and a payload, enhancing the specific recognition and delivery of both components and constituting an active agent for MDM2 regulation. Following SNA endocytosis by RB cells, siRNA and NVP-CGM097 were released from the SNA particles by glutathione, which synergistically blocked the MDM2-p53 pathway, increasing p53 protein content and inducing cell apoptosis. This study showed a potent antitumor effect following intravitreal injection of SNAs in Y79 tumor-bearing mice through clinical manifestation and tumor pathological analysis. In hematological analysis and hepatotoxicity assays, SNAs were safer for mice than melphalan, the favored drug for treating RB in clinical practice. Our results illustrated the potential of intravitreally injected SNAs as a precision medicine for treating RB.

Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling.

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated ß-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration.

Introduction: Photoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations. Methods: We established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein-protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug-gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes. Discussion: Our findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

Retinal Artery Angles in High Axial Myopia and Its Relationship With Visual Function.

Purpose: To evaluate the retinal artery angles in high axial myopia and assess the correlation with other morphometric and functional parameters. Methods: This cross-sectional study included 112 eyes of 112 patients with high axial myopia. Based on axial length (AL), the participants were divided into three groups: group 1 (26 ≤ AL < 28 mm), group 2 (28 ≤ AL < 31 mm), and group 3 (≥31 mm). Scanning laser ophthalmoscopy imaging was used to analyze the retinal artery angle (Yugami correlated angle [YCA]). Retinal vascular densities (VDs) in both superficial capillary plexuses (SCPs) and deep capillary plexuses were evaluated. Fixation behavior, including retinal mean sensitivity (MS), macular fovea 2°, 4° fixation rate (P1, P2), and 68.2% bivariate contour ellipse area, were analyzed by microperimetry. Finally, the correlation between YCAs and AL, VDs, best-corrected visual acuity (BCVA), and fixation behavior was assessed. Results: The YCAs showed significant differences among the three groups (all P < 0.001, respectively). Compared to group 1, the YCA decreased in group 2 (P < 0.001) and continued to decrease in group 3 (P = 0.043). The correlation analysis revealed that smaller YCAs (YCA, YCA1/2, YCA1/4) were positively correlated with the longer AL (ρ = 0.580, 0.545, 0.448, P < 0.001) and lower VDs in any sector in SCPs (all P ≤ 0.05). Furthermore, smaller YCAs were positively correlated with decreased BCVA (ρ = 0.392, 0.387, 0.262; all P < 0.001) and reduced MS (ρ= 0.300, 0.269, 0.244; all P < 0.05). Conclusions: Smaller YCAs were correlated with longer AL, lower VD in SCP, decreased BCVA, and reduced MS. The YCAs might reflect vascular deformation caused by axial elongation and could potentially be useful in predicting visual function in high axial myopia. Translational Relevance: The quantitative analysis of YCAs in fundus photography holds potential clinical value in predicting visual function in high axial myopia.

Surgical Outcomes of Myopic Foveoschisis According to the ATN Classification System.

INTRODUCTION: This study compared the surgical outcomes in eyes with myopic foveoschisis (MF) according to the recently developed ATN classification system. METHODS: This was an observational case series of 64 consecutive eyes that underwent vitrectomy for MF. Eyes were classified into severe myopic maculopathy (MM) (n = 43) and non-severe MM (n = 21) groups according to the ATN classification system. The primary outcome measures constituted best-corrected visual acuity (BCVA) and anatomical changes. RESULTS: In total, BCVA improved from 0.97 to 0.53 (P < 0.001) after surgery. The ATN score was significantly lower in the eyes with vision improvement than those without vision improvement (P < 0.001). In the subgroup, BCVA improved from 0.79 to 0.28 in the non-severe MM group (P < 0.001), and improved from 1.05 to 0.65 in the severe MM group (P = 0.001) after surgery. The non-severe MM group achieved better postoperative BCVA (P = 0.001) and were more likely to gain vision improvement (P < 0.001) after surgery compared with the severe MM group. Anatomical success was achieved in 62 of the 64 eyes (96.88%). Two eyes with anatomical failure developed full-thickness macular holes postoperatively; both were in the severe MM group. CONCLUSIONS: For patients with MF, different severity of MM based on ATN classification could lead to a significantly different prognosis after surgery. For patients with high ATN scores, the operative decision should be made cautiously for the worse anatomical and visual prognosis. ATN system is instructive in making operative proposals for MF.

On the basis of the newly developed ATN classification system, we found significant differences in postoperative visual acuity, the rate of vision improvement, and the rate of primary retinal reattachment after vitrectomy between the severe and non-severe myopic maculopathy groups in patients with myopic foveoschisis.