Inflammasomes in Cell Death in FTMH, ERM, and RRD

NCT ID: NCT03332758

Last Updated: 2018-08-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

41 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-09-08

Study Completion Date

2018-05-01

Brief Summary

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Prospective study evaluating the role of inflammasomes in cell death in retinal detachment, full thickness macular hole, and epiretinal membrane. The investigators are collecting vitreous and subretinal fluid samples from patients with these conditions and evaluating activity of the inflammasome pathway with established assays.

Detailed Description

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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.

Conditions

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Retinal Detachment Full Thickness Macular Hole Epiretinal Membrane

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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RD treated with vitrectomy

Vitreous fluid from retinal detachment treated with pars plana vitrectomy

Pars plana vitrectomy

Intervention Type PROCEDURE

Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.

RD treated with external drainage

Subretinal fluid from retinal detachment treated with external drainage.

External drainage

Intervention Type PROCEDURE

Standard of care treatment for retinal detachment.

Macular holes treated with vitrectomy

Vitreous fluid from patients treated for macular hole

Pars plana vitrectomy

Intervention Type PROCEDURE

Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.

ERM treated with vitrectomy

Vitreous fluid from patients treated for epiretinal membrane

Pars plana vitrectomy

Intervention Type PROCEDURE

Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.

Interventions

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Pars plana vitrectomy

Standard of care treatment for retinal detachment, macular hole, or epiretinal membrane.

Intervention Type PROCEDURE

External drainage

Standard of care treatment for retinal detachment.

Intervention Type PROCEDURE

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mid Atlantic Retina

OTHER

Sponsor Role collaborator

Allen C. Ho, MD

OTHER

Sponsor Role lead

Responsible Party

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Allen C. Ho, MD

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Allen C Ho, MD

Role: PRINCIPAL_INVESTIGATOR

MidAtlantic Retina

Locations

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MidAtlantic Retina-Wills Eye Hospital

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Murakami Y, Notomi S, Hisatomi T, Nakazawa T, Ishibashi T, Miller JW, Vavvas DG. Photoreceptor cell death and rescue in retinal detachment and degenerations. Prog Retin Eye Res. 2013 Nov;37:114-40. doi: 10.1016/j.preteyeres.2013.08.001. Epub 2013 Aug 28.

Reference Type BACKGROUND
PMID: 23994436 (View on PubMed)

Kataoka K, Matsumoto H, Kaneko H, Notomi S, Takeuchi K, Sweigard JH, Atik A, Murakami Y, Connor KM, Terasaki H, Miller JW, Vavvas DG. Macrophage- and RIP3-dependent inflammasome activation exacerbates retinal detachment-induced photoreceptor cell death. Cell Death Dis. 2015 Apr 23;6(4):e1731. doi: 10.1038/cddis.2015.73.

Reference Type BACKGROUND
PMID: 25906154 (View on PubMed)

Other Identifiers

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17-660E

Identifier Type: -

Identifier Source: org_study_id

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