Ocular Gene Therapy: A Comprehensive Review with Special Focus on Inflammatory and Immune Responses

In recent years, there has been an increasing focus on researching gene therapy. The eye is a subject of high interest in the advancement of gene therapy, since it is one of the rare body organs where gene therapy has been sanctioned by the Food and Drug Administration. Nevertheless, the immune and inflammatory reactions linked to it can make the treatment ineffective or even detrimental. This is especially crucial for the eye, as it is susceptible to inflammation. The intensity of the immune and inflammatory reactions varies depending on the selection of vector and method of delivery. Additionally, the majority of preclinical and clinical research has demonstrated a relationship between the dosage of the vector and the level of humoral response and ocular inflammation. The method of delivery directly influences the level of immune and inflammatory responses. Subretinal administration leads to decreased fluid pressure in the eye and exhibits a superior reaction compared to the intravitreal method. Hence, certain research has shown that subretinal administration could result in a more significant impact. Response that causes inflammation. However, clinical trials utilizing viral vectors injected into the eye have documented numerous instances of vision impairment from intense inflammation within the eye, while delivering genes through the suprachoroidal route has been found to trigger a milder immune response than intravitreal injection.Hence, the suprachoroidal space does not have the same immune protection as the subretinal space. The following ophthalmic gene therapy are mild, and both clinical and preclinical research suggests that these can be managed using topical, localized, or systemic steroids.