Abstract
Background: X-linked retinoschisis is a retinovitreal disorder primarily affecting males, starting in childhood. Over time, patients experience deterioration of vision due to the lack of retinoschisin-1 function. In clinical trials performing intravitreal gene delivery in those affected by this disorder, ocular inflammation was observed, which may have masked efficacy. A subsequent study focusing on analyzing the populations of peripheral blood mononuclear cells and cytokines in adults with this disease reported aberrant dendritic cell numbers and cytokine levels in peripheral blood, indicating that adults with this disease may have an altered baseline immunity. Whether the aberrant peripheral immunity in affected adults was a consequence of advanced eye pathology remained unclear. This study focuses on analyzing the populations of blood lymphocyte subsets in children aged 0 to 7 years with X-linked retinoschisis and age-matched controls using flow cytometry. Results: The fractions of lymphocyte subsets that were CD16a+/CD56+, namely natural killer cells, were significantly lower in blood samples from children with X-linked retinoschisis. In children with X-linked retinoschisis, the fractions of CD3+/CD4 + T cells were higher, and the fractions of CD3 + CD8 + T cells were lower, despite having the same amounts of total CD3 + T cells within their lymphocyte populations. This resulted in a significantly greater CD4/CD8 ratio in children with X-linked retinoschisis compared to age-matched controls. Conclusions: Alterations were found in blood lymphocyte compositions of children with X-linked retinoschisis within both innate and adaptive immune axes. Some alterations including an elevation of CD4/CD8 ratio in X-linked retinoschisis mirror those previously found in adult patients with this disease. The fact that these abnormalities were present early in this disease indicates that retinoschisin-1 may play a role in regulating immunity in addition to retinal structure. The findings may have implications for future treatments such as ocular gene delivery.