Inflammasomes in Cell Death in FTMH, ERM, and RRD

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.

Inclusion Criteria:

1. Patient of the Wills Eye Hospital Retina service and Mid-Atlantic Retina offices.

2. Volunteer patients age 18 years and older.

3. Healthy enough to participate in the study.

4. Willing and able to consent to participation in the study.

5. Diagnosis of rhegmatogenous retinal detachment treated with external drainage of
subretainl fluid, rhegmatogenous retinal detachment treated with pars plana
vitrectomy, or full thickness macular hole treated with pars plana vitrectomy

Exclusion Criteria:

1. Presence of tractional retinal detachment

2. History of trauma

3. Presence of proliferative vitreoretinopathy

4. History of prior retinal detachment repair or any prior retina surgery or laser
treatment e. Any preexisting retinal disease (including diabetic retinopathy, age
related macular degeneration, retinal vein or artery occlusion, other retinal vascular
disease, inherited retinal degeneration, uveitis)