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Apoptosis in proliferative vitreoretinopathy
Ibraheem El Ghrably1, Des G Powe, Gavin Orr
1Division of Ophthalmology and Visual Sciences, University Hospital, Nottingham, United Kingdom.
Purpose:
To study the involvement of apoptosis using different apoptosis markers in PVR pathogenesis.
Methods:
The presence of mRNA coding for Fas, Fas ligand (FasL), and TNF-related apoptosis inducing ligand (TRAIL) was investigated in vitreous samples from 46 consecutive patients-25 with PVR, 11 with retinal detachment (RD) not complicated by PVR, and 10 with macular hole (MH)-using RT-PCR. From previously examined vitreous samples, 21 PVR, 9 RD, and 10 MH were examined for their levels of TGF-beta2 protein with sandwich ELISA kits. Five epiretinal membranes excised from five patients with PVR were also examined for apoptotic cell death using the terminal deoxytransferase (TdT) mediated dUTP-biotin nick end labeling (TUNEL) technique.
Results:
FAS mRNA was detected in 72% of patients with PVR, 55% of patients with RD and 20% of patients with MH. TRAIL mRNA was detected in 67% of patients with PVR, 89% of patients with RD, and 20% of patients with MH. FasL mRNA was detected in 20% of patients with PVR, 9% of patients with RD, and 10% of patients with MH. The median levels of Fas and TRAIL mRNA were significantly higher (P < 0.05) in patients with PVR than in those with MH hole but between patients with PVR and those with RD the difference was not significant (P > 0.05). A significant difference was detected between RD and MH for TRAIL mRNA levels (P = 0.008). For FasL, no significant difference between groups was found. TGF-beta2 was detected in all investigated vitreous samples. A significant difference was found between the PVR and MH groups (P = 0.001) and between the RD and MH groups (P = 0.004), but not between the PVR and RD groups (P < 0.05). The level of TGF-beta2 was significantly correlated to the level of TRAIL mRNA (r = 0.86), but no correlation was found between TGF-beta2 and Fas mRNA levels (r = 0.21). Four of five examined PVR epiretinal membranes showed positive staining for apoptotic cells using the TUNEL technique.
Conclusions:
Apoptosis is one of the mechanisms that is involved in PVR pathogenesis. Different apoptosis markers suggest different pathways occur in PVR, including Fas/FasL, TRAIL, and TGF-beta2 mediated processes.
Insights
Apoptosis plays a role in proliferative vitreoretinopathy (PVR) pathogenesis. Key apoptosis markers like Fas/FasL, TRAIL, and TGF-beta2 indicate distinct pathways involved in PVR development.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Proliferative vitreoretinopathy (PVR) is a severe complication of retinal detachment.
- Understanding the molecular mechanisms underlying PVR pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the involvement of apoptosis in PVR pathogenesis.
- To analyze the expression of different apoptosis markers in patients with PVR.
Main Methods:
- RT-PCR was used to detect mRNA for Fas, Fas ligand (FasL), and TNF-related apoptosis inducing ligand (TRAIL) in vitreous samples.
- TGF-beta2 protein levels were measured using ELISA.
- Apoptotic cells in epiretinal membranes were identified using the TUNEL technique.
Main Results:
- FAS and TRAIL mRNA levels were significantly higher in PVR patients compared to macular hole patients.
- TGF-beta2 levels were elevated in PVR and retinal detachment (RD) groups compared to the macular hole group.
- Apoptotic cells were detected in epiretinal membranes from PVR patients.
Conclusions:
- Apoptosis is implicated as a mechanism in PVR pathogenesis.
- The findings suggest that Fas/FasL, TRAIL, and TGF-beta2 mediated pathways are involved in PVR.
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