Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye’s accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is related to the pathogenesis of various retinopathies including age-related macular degeneration (AMD). Oxidative stress is the major factor that induces degeneration of RPE cells associated with the etiology of AMD. Sodium iodate (NaIO₃) generates intracellular reactive oxygen species (ROS) and is widely used to establish a model of AMD due to the selective induction of retinal degeneration. This study was performed to clarify the effects of multiple NaIO₃-stimulated signaling pathways on EMT in RPE cells. The EMT characteristics in NaIO₃-treated human ARPE-19 cells and RPE cells of the mouse eyes were analyzed. Multiple oxidative stress-induced modulators were investigated and the effects of pre-treatment with Ca²⁺ chelator, extracellular signal-related kinase (ERK) inhibitor, or epidermal growth factor receptor (EGFR) inhibitor on NaIO₃-induced EMT were determined. The efficacy of post-treatment with ERK inhibitor on the regulation of NaIO₃-induced signaling pathways was dissected and its role in retinal thickness and morphology was evaluated by using histological cross-sections and spectral domain optical coherence tomography. We found that NaIO₃ induced EMT in ARPE-19 cells and in RPE cells of the mouse eyes. The intracellular ROS, Ca²⁺, endoplasmic reticulum (ER) stress marker, phospho-ERK, and phospho-EGFR were increased in NaIO₃-stimulated cells. Our results showed that pre-treatment with Ca²⁺ chelator, ERK inhibitor, or EGFR inhibitor decreased NaIO₃-induced EMT, interestingly, the inhibition of ERK displayed the most prominent effect. Furthermore, post-treatment with FR180204, a specific ERK inhibitor, reduced intracellular ROS and Ca²⁺ levels, downregulated phospho-EGFR and ER stress marker, attenuated EMT of RPE cells, and prevented structural disorder of the retina induced by NaIO₃. ERK is a crucial regulator of multiple NaIO₃-induced signaling pathways that coordinate EMT program in RPE cells. Inhibition of ERK may be a potential therapeutic strategy for the treatment of AMD.

Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo. Numerous investigations have reported an increased BPPV incidence in females and in the aged population. The hormonal characteristics of BPPV patients have not been previously investigated. This study aimed to determine the risk of BPPV in relation to menopause in a population-based study. Materials and Methods: This retrospective population-based study was designed to use a nationwide longitudinal health insurance database to follow and analyze the incidence of and protective factors against BPPV in a Taiwanese population. Data Analyses: Univariate and multivariate analyses were performed to calculate the adjusted hazard ratio (aHR) for the incidence of BPPV using Cox-proportional regression models. Results: In the multivariate analyses, we found that older people (older than 65 years old) were more prone to develop BPPV (aHR: 5.37, 95% CI: 0 4.83–5.97, p < 0.001). The risk of BPPV was analyzed in two specific age subgroups of elderly females. Results revealed that in both age groups (45–65 years old and >65 years old), patients who took estrogen for menopausal syndromes had a significantly lower incidence of BPPV (aHR; 0.01, 95% CI: 0.06–0.23, p < 0.001). Conclusion: Our study provides a novel etiology and possible treatment method for the prevention of BPPV. Further studies may focus on the pathophysiological mechanism of estrogen in BPPV patients and the development of new drugs for the prevention and treatment of BPPV.

Artificial intelligence (AI), Internet of Things (IoT), and telemedicine are deeply involved in our daily life and have also been extensively applied in the medical field, especially in ophthalmology. Clinical ophthalmologists are required to perform a vast array of image exams and analyze images containing complicated information, which allows them to diagnose the disease type and grade, make a decision on remedy, and predict treatment outcomes. AI has a great potential to assist ophthalmologists in their daily routine of image analysis and relieve their work burden. However, in spite of these prospects, the application of AI may also be controversial and associated with several legal, ethical, and sociological concerns. In spite of these issues, AI has indeed become an irresistible trend and is widely used by medical specialists in their daily routines in what we can call now, the era of AI. This review will encompass those issues and focus on recent research on the AI application in ophthalmology and telemedicine.

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.