Nanoparticle-Based gene therapy strategies in retinal delivery.

Vision loss and blindness are significant issues in both developed and developing countries. There are a wide variety of aetiologies that can cause vision loss, which are outlined in this review. Although treatment has significantly improved over time for some conditions, nearly half of all people with vision impairment are left untreated.

Polymer-Based Nanoparticles with Probucol and Lithocholic Acid: A Novel Therapeutic Approach for Oxidative Stress-Induced Retinopathies.

Oxidative stress is pivotal in retinal disease progression, causing dysfunction in various retinal components. An effective antioxidant, such as probucol (PB), is vital to counteract oxidative stress and emerges as a potential candidate for treating retinal degeneration. However, the challenges associated with delivering lipophilic drugs such as PB to the posterior segment of the eye, specifically targeting photoreceptor cells, necessitate innovative solutions.

AAV capsid bioengineering in primary human retina models.

Adeno-associated viral (AAV) vector-mediated retinal gene therapy is an active field of both pre-clinical as well as clinical research. As with other gene therapy clinical targets, novel bioengineered AAV variants developed by directed evolution or rational design to possess unique desirable properties, are entering retinal gene therapy translational programs. However, it is becoming increasingly evident that predictive preclinical models are required to develop and functionally validate these novel AAVs prior to clinical studies.

Compensatory Cone-Mediated Mechanisms in Inherited Retinal Degeneration Mouse Models: A Functional and Gene Expression Analysis.

The retina undergoes compensatory changes in response to progressive photoreceptor loss/dysfunction; however, studies of inherited retinal diseases (IRDs) often lack a temporal connection between gene expression and visual function. Here, we used three mouse models of IRD - Cnga3, Pde6c, and Rd1 - to investigate over time the effect of photoreceptor degeneration, particularly cones, on visual function and gene expression. Changes to gene expression include increases in cell survival and cell death genes in Pde6c before significant cell loss, as well as an increase in cone-specific genes in the Rd1 at the peak of rod death.

Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy.

Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite individual IRDs (Inherited retinal disease) being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6c mouse model of achromatopsia, a cone-specific vision loss IRD (Inherited retinal disease), to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival.

Primary and Secondary Cone Cell Death Mechanisms in Inherited Retinal Diseases and Potential Treatment Options.

Inherited retinal diseases (IRDs) are a leading cause of blindness. To date, 260 disease-causing genes have been identified, but there is currently a lack of available and effective treatment options. Cone photoreceptors are responsible for daylight vision but are highly susceptible to disease progression, the loss of cone-mediated vision having the highest impact on the quality of life of IRD patients.

Validating Fluorescent Chrnb4.EGFP Mouse Models for the Study of Cone Photoreceptor Degeneration.

Purpose: To validate the application of a known transgenic mouse line with green fluorescent cones (Chrnb4.EGFP) to study cone photoreceptor biology and function in health and disease.

Methods: Chrnb4.