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A novel function of p53: a gatekeeper of retinal detachment.

ABSTRACT: Proliferative vitreoretinopathy (PVR) is a blinding disease associated with rhegmatogenous retinal detachment, for which there is no satisfactory treatment. Surgery helps in many cases, but, to our knowledge, there are no pharmacological approaches to reduce PVR risk. We report that suppressing expression of p53 was a required event in two assays of PVR (namely, platelet-derived growth factor receptor ?-mediated contraction of cells in a collagen gel and retinal detachment in an animal model of PVR). Furthermore, preventing the decline in the level of p53 with agents such as Nutlin-3 protected from retinal detachment, which is the most vision-compromising component of PVR. Finally, Nutlin-3 may be effective in the clinical setting because it prevented human PVR vitreous-induced contraction of cells isolated from a patient PVR membrane. These studies identify Nutlin-3 as a potential PVR prophylaxis.

SUBMITTER: Lei H

PROVIDER: S-EPMC3432438 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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A novel function of p53: a gatekeeper of retinal detachment.

Lei Hetian H Rheaume Marc-Andre MA Cui Jing J Mukai Shizuo S Maberley David D Samad Arif A Matsubara Joanne J Kazlauskas Andrius A

The American journal of pathology 20120901 3

Proliferative vitreoretinopathy (PVR) is a blinding disease associated with rhegmatogenous retinal detachment, for which there is no satisfactory treatment. Surgery helps in many cases, but, to our knowledge, there are no pharmacological approaches to reduce PVR risk. We report that suppressing expression of p53 was a required event in two assays of PVR (namely, platelet-derived growth factor receptor α-mediated contraction of cells in a collagen gel and retinal detachment in an animal model of ...[more]

PMID: 22901751

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Novel use of Finesse Flex loop for macular hole retinal detachment.

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Project description:Existing surgical modes for retinal detachment are elaborate and extremely complex. We have treated 20 cases of rhegmatogenous retinal detachment with pneumatic retinopexy which is Iess time consuming and does not require hospitalization. After pneumatic retinopexy reattachment of retina was achieved in 15 (75%) eyes. In 2 eyes retinal reattachment was achieved after repeating intravitreal injection of sulphur hexafluoride gas. Remaining 3 eyes were secondarily treated with scleral buckle surgery. One case needed vitreoretinal surgery. In pneumatic retinopexy there is minimum tissue handling and functional results are good.

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Pseudophakic retinal detachment in young-aged patients.

Project description:ObjectiveTo investigate the incidence and risk factors for retinal detachment (RD) after cataract surgery or refractive lens exchange (RLE) in patients aged below 61 years.MethodsRetrospective medical chart review of 7,886 patients (13,925 eyes) who underwent cataract surgery or RLE. Patients aged below 61 years were selected. Age, gender, axial length, follow-up times, and the occurrence of RD were recorded. Additional characteristics documented for RD cases were: history of RD, preexisting retinal findings, laser capsulotomy, status of macula at RD, date and details of RD.ResultsFrom a total of 421 patients (677 eyes) aged below 61 years 24 cases of RD were identified, resulting in an overall cumulative incidence per eyes of 3.55%. The mean follow-up time was 45 ± 32.8 months. Ninety-two % of all RDs occurred within 3.6 years from surgery. Axial length had a significant effect on the risk of RD after cataract/ RLE surgery (HR = 1.42, P = 0.0001, 95% CI 1.19-1.69). The highest incidence of RD occurred in the subgroup of 25 to 28.9 mm axial length (10.2%). With an increase in age of ten years, the hazard of postoperative RD was not significantly increased by a factor of 1.50 (P = 0.286, 95% CI 0.71-3.15). The highest incidence of RD occurred in patients aged 50-54 years (5.39%). Compared to females, males had an almost twofold not significant risk of postoperative RD (HR = 1.96, P = 0.123, 95% CI 0.83-4.63). None of the RD cases had a history of RD.ConclusionsAxial length is a significant risk factor for pseudophakic RD. The need for cataract surgery or RLE should be carefully considered in patients with axial lengths between 25 and 29 mm, aged 50-54 years, in males, and in case of preexisting retinal findings.

| S-EPMC5578613 | biostudies-literature

Biomarkers for PVR in rhegmatogenous retinal detachment.

Project description:PurposeVarious profibrotic and proinflammatory cytokines have been found upregulated in uncomplicated primary retinal detachment (pRD), but without providing a uniform picture. Here, we compare the cyto- and chemokine profiles in pRD with and without proliferative vitreoretinopathy (PVR) in an attempt to unravel relevant differences not in single cytokines, but in the cytokine profiles at diagnosis.MethodsUndiluted vitreous fluid (VF) was obtained at the beginning of surgery from 174 eyes with pRD without relevant PVR (maximally grade B; group 1; n = 81) and with moderate or advanced PVR requiring a gas tamponade (group 2; n = 49) or silicon oil filling (group 3; n = 44). VF of eyes undergoing macular hole (MH) surgery served as controls (group 4; n = 26). Forty-three cytokines were quantified in parallel using a multiplex cytokine analysis system (Bioplex). For all comparisons we applied Holm's correction to control for multiple comparisons.Results44.9% of group 2 eyes presented grade C1 and 55.1% C2-C3, whereas 86.4% of group 3 eyes exhibited a PVR grade of C2-D. CCL19 was the only cytokine that displayed higher concentrations in the vitreous of eyes with PVR C1 compared to lower PVR grades. Eyes with PVR C2-D showed higher levels of CCL27, CXCL6, IL4, IL16, CXCL10, CCL8, CCL22, MIG/CXCL9, CCL15, CCL19, CCL 23 and CXCL12 compared to controls. Interestingly, no difference of cytokine levels was detected between C1 and C2-D PVR.ConclusionsCCL19 may represent a potential biomarker for early PVR progression that holds promise for future diagnostic and therapeutic applications.

| S-EPMC6447182 | biostudies-literature

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