Expression of clusterin in Müller cells of the rat retina after pressure‐induced ischemia

Abstract

We have investigated the expression and cellular localization of clusterin in the rat retina following ischemia induced by transiently increasing the intraocular pressure. In the normal retina, weak clusterin immunoreactivity was visible in Müller cell profiles located in the inner nuclear layer. Following ischemia and reperfusion, strong immunoreactivity appeared in Müller cell somata and processes up to 3 days postlesion. Quantitative evaluation by immunoblotting confirmed that clusterin expression continuously increased and showed a peak value at 3 days after ischemic injury (to 1300% of control levels), and then decreased again to 400% of controls at 4 weeks postlesion. Immunocytochemistry using antisera against clusterin or glutamine synthase combined with the TUNEL method or immunocytochemistry using antisera activated caspase 3 and electron microscopy revealed that some clusterin-labeled Müller cells underwent apoptotic cell death. Our findings demonstrate that some Müller cells die by apoptosis, and suggest that clusterin produced and released by Müller cell may play an important role in the pathogenesis of ischemic injury in the rat retina.

Proteome profiling of vitreoretinal diseases by cluster analysis

“…In the RRD and PVR samples, in comparison to the NPDR and PDR samples, there were significantly higher levels of PEDF, CLU, CTSD, and TTR detected. All of these proteins were reported to exist in RPE cells or glial cells that play an important role in pathogenesis of RRD and PVR [53][54][55][56][57][58][59][60][61][62][63][64], eloquently exhibiting the breakdown of retinal integrity and the flowing in of subretinal fluids into the vitreous samples.…”

“…In addition, upregulation of CLU has been reported in response to pathological conditions, such as Alzheimer's disease [67], spinal cord injury [68], and retinal degeneration [69]. It has also been reported that the CLU gene was up-regulated in cultured RPE cells in early passage compared to later passages [57] and that the expression of CLU protein in Müller cells was up-regulated by the pressure-induced ischemic injury in the rat retina [58]. The primary event of PVR is the formation of a retinal break.…”

Clusterin Deficiency in Eyes with Pseudoexfoliation Syndrome May Be Implicated in the Aggregation and Deposition of Pseudoexfoliative Material

“…Aqueous levels of clusterin were significantly decreased in PEX syndrome (3-fold; *P Ͻ 0.001) and displayed an increase in PEX-associated OAG (1.6-fold; **P Ͻ 0.02) compared with cataract. Ocular clusterin has been functionally implicated primarily in retinal (patho)physiology; increased expression has been shown in the retina of rds mutant mice, 38 in the retina of rats after light-induced photoreceptor degeneration 13 or ischemia and reperfusion injury, 12 and in human patients with various retinal dystrophies (e.g., retinitis pigmentosa). 11,35 Reduced expression of clusterin has been reported only in the keratinized conjunctival epithelium in severe ocular surface diseases, suggesting that this molecule is important for the maintenance of the ocular surface epithelium.…”

Expression of the Na+-K+-2Cl--Cotransporter 2 in the Normal and Pressure-Induced Ischemic Rat Retina

“…We raised intraocular pressure to 120 mmHg for 60 minutes. According to prior studies that used a similar experimental paradigm, cellular reaction to ischemic insult has a peak at 3 days [22,23]. …”