Abstract: Age-related macular degeneration (AMD) remains a leading cause of severe visual impairment in developing countries. Although dry-type AMD and geographic atrophy (GA) are progressive conditions with the associated decrease of visual functions, no well-established treatment regimen was proposed for the disease. Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents, but frequent injections are a major issue for the affected patients. Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD, but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence. Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices. Simultaneously, gene therapy for dry and wet AMD is widely studied. Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease, many challenges exist in the way of its broad impact on the ocular health of AMD patients.
Background: The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy (DR). It ensures an experimental overview with more complete respect to isolate cells and reduce problems in terms of accessibility and management with respect to in vivo model. In particular, it allows the evaluation of the relationship between retinal cells in response to the typical stressors involved in DR pathogenesis.
Methods: Ex vivo retinal fragments derived from 3- to 5-week-old C57BL/6J mice. In particular, after dissection, the retina is cut into 4 separate fragments and transferred onto inserts placed with ganglion cells up. Once in culture, the explants could be treated in stress conditions typical of DR. In particular, this study protocol describes the procedure for the preparation and the culture of retinal explants with specific metabolic stressors such as high glucose (HG), advanced glycation end product (AGE), and oxidative stress (OS). In the end, this paper provides the protocols to perform molecular analyses in order to evaluate the response of retinal explants to stress and/or neuroprotective treatments.
Discussion: The cultured retinal explants represent an ex vivo experimental model to investigate the molecular mechanisms involved in neurovascular diseases such as DR. Moreover, they could be useful to test the effect of neuroprotective compounds in response to metabolic stressors in a fewer time respect to an in vivo model. In conclusion, retinal explants in culture represent a valuable experimental model to conduct further studies to better understand the pathophysiology of DR.
Background and Objective: Subthreshold laser therapy has emerged as a therapeutic alternative to traditional laser photocoagulation for certain ophthalmic diseases including central serous chorioretinopathy (CSCR), diabetic macular edema (DME), macular edema secondary to branch retinal vein occlusion (BRVO), and age-related macular degeneration (AMD). The objective of this paper is to review and discuss the clinical applications of subthreshold laser and the mechanisms of different subthreshold laser techniques including subthreshold micropulse laser (SMPL), selective retina therapy (SRT), subthreshold nanosecond laser (SNL), endpoint management (EpM), and transpupillary thermotherapy (TTT).
Methods: A narrative review of English literature and publicly available information published before November 2021 from literature databases and computerized texts. We discuss the currently available subthreshold laser systems and the advancements made to perform different subthreshold laser techniques for various ophthalmic diseases. We highlight various clinical studies and therapeutic techniques that have been conducted to further understand the effectiveness of subthreshold laser in the clinical setting. We conclude the article by covering emerging subthreshold laser systems that are currently being developed for future clinical use. The PubMed database was utilized for peer-reviewed articles and pertinent information on subthreshold systems was cited from publicly available online websites covering specific systems.
Key Content and Findings: Various subthreshold laser systems have been developed to treat certain retinal diseases. Several systems are currently in development for future clinical applications.
Conclusions: While conventional laser photocoagulation has been effective in treating various retinal diseases, subthreshold laser systems aim to provide a therapeutic effect without visible signs of damage to the underlying tissue. This technology may be particularly effective in treating macular disorders. Further clinical studies are needed to evaluate their role in the management of retinal diseases.
