Inflammasomes in Cell Death in Macular Hole, Epiretinal Membrane, and Rhegmatogenous Retinal Detachment

Photoreceptor cell death is the main cause of vision loss in many retinal disorders, including retinal detachment (RD). While apoptosis is the most studied form of cell death, the investigators believe patients with RDs may have photoreceptor cell death from a distinct pathway of programmed cell death called pyroptosis which also involves an inflammatory response. Pyroptosis is distinct from apoptosis in that it requires the activation of a protein oligomer complex called an inflammasome. The inflammasome is a pro-inflammatory complex composed of apoptosis-associated speck-like protein containing a CARD (ASC), nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor (NLR) family or pyrin and HIN domain (PYHIN) family, and caspase-11. Activation of the inflammasome complex leads to activation of capspase 1 proteolytic activity to cleave and synthesize IL-1β and IL-18. As such the investigators believe inflammasomes and its activated products may play a strong role in the inflammatory and cell death pathway for photoreceptor cells in human retina. Studies using animal models of RD have already confirmed the presence of IL-1β activation2, however, the presence of IL-18 needs to be confirmed in human detached retinas. In a study performed on the detached retinas in mice, researchers were able to show activation of inflammasomes leading to photoreceptor cell death. While researchers are unable to determine the cellular source of the inflammasomes they were able to show that activation inflammasomes closely follows animal models. Currently there is no method to rescue photoreceptors cells from the mediated cell death pathway despite surgical intervention. Thus, current visual prognosis and prevention of further photoreceptor loss due to a RD is likely dependent on the time of surgical intervention before further detachment and further cell death can occur. As such, the purpose of this current study is to confirm the presence of inflammasome activation as well as the synthesis of its products, IL-1β and IL-18, in patients with rhegmatogenous retinal detachments. Both inflammasomes and its products IL-1β and IL-18 may be involved in cell pyroptosis, a programmed cell death distinct from apoptosis. Due to a lack of treatment for the rescue of photoreceptor cells from cell death after a retinal detachment, this study can provide novel strategies to inhibit cell death.