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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-08-2005 | Laboratory Investigation

Protein kinase C expression in the rabbit retina after laser photocoagulation

Authors: Fredrik Ghosh, Karin Gjörloff

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 8/2005

Abstract

Background

Laser photocoagulation is a well-established treatment for diabetic retinopathy but the mechanism behind its effectiveness has not been elucidated. The protein kinase C (PKC) family is a group of enzymes which has been the subject of extensive interest in clinically related research since the advent of its role in the pathogenesis of diabetic retinopathy. With this study we wanted to explore whether PKC expression is altered in the retina after laser photocoagulation.

Methods

Normal rabbit eyes were treated with laser photocoagulation of varying intensity and examined after 30 min to 7 weeks. Treated and untreated regions of the retina were investigated histologically with the MC5 monoclonal antibody against PKC. Labeling for glial fibrillary acidic protein (GFAP), as well as hematoxylin and eosin (H&E) staining was also performed to assess the laser-induced trauma.

Results

In the normal retina, the MC5 antibody labeled rod bipolar cells and photoreceptor outer segments corresponding to PKC alpha. A translocated PKC expression with labeling concentrated in the rod bipolar terminals was seen in specimens examined 30 min after laser treatment, and after 1 week, no expression was seen in any part of the retina. After 2 weeks, PKC expression again indicated a translocated labeling pattern. After 5 weeks, labeling was found only in rod bipolar terminals in the peripheral retina. When comparing high- and low-intensity laser treatment 7 weeks postoperatively, no labeling was found in the high intensity-treated retinas, whereas low intensity-treated eyes displayed a near-normal labeling pattern. H&E staining revealed focal neuroretinal edema immediately after laser treatment, also in untreated areas. At later stages, destruction of the outer nuclear layer and migration of pigment epithelial cells in laser-lesioned areas was seen. GFAP-labeled Müller cells were seen 1 week postoperatively in the entire retina. Labeling after this time decreased, but was still present in laser spots after 5 and 7 weeks.

Conclusions

Laser photocoagulation alters the expression of PKC in the entire normal rabbit retina. The response follows a temporal pattern and is also related to laser intensity. These findings may help to explain the high efficacy of laser treatment in diabetic retinopathy.

Aiello LP (2002) The potential role of PKC beta in diabetic retinopathy and macular edema. Surv Ophthalmol 47:263–269

Bignami A, Dahl D (1979) The radial glia of Muller in the rat retina and their response to injury. An immunofluorescence study with antibodies to the glial fibrillary acidic (GFA) protein. Exp Eye Res 28:63–69

Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Caldwell RW (2003) Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev 19:442–455

Curtis TM, Scholfield CN (2004) The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy. Diabetes Metab Res Rev 20:28–43

Early Treatment Diabetic Retinopathy Study Research Group (1985) Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol 103:1796–1806

Ghazi-Nouri SM, Assi A, Limb GA, Scott RA, von Bussmann K, Humphrey I, Luthert PJ, Charteris DG (2003) Laser photocoagulation alters the pattern of staining for neurotrophin-4, GFAP, and CD68 in human retina. Br J Ophthalmol 87:488–492

Greferath U, Grünert U, Wässle H (1990) Rod bipolar cells in the mammalian retina show protein kinase c-like immunoreactivity. J Comp Neurol 301:433–442

Higgins KE, Meyers SM, Jaffe MJ, Roy MS, de Monasterio FM (1986) Temporary loss of foveal contrast sensitivity associated with panretinal photocoagulation. Arch Ophthalmol 104:997–1003

Koistinaho J, Sagar SM (1994) Localization of protein kinase C subspecies in the rabbit retina. Neurosci Lett 177:15–18

10.

Leibu R, Davila E, Zemel E, Bitterman N, Miller B, Perlman I (1999) Development of laser-induced retinal damage in the rabbit. Graefe Arch Clin Exp Ophthalmol 237:991–1000

11.

Lu Z, Liu D, Hornia A, Devonish W, Pagano M, Foster DA (1998) Activation of protein kinase C triggers its ubiquitination and degradation. Mol Cell Biol 18:839–845

12.

Midena E, Segato T, Bottin G, Piermarocchi S, Fregona I (1992) The effect on the macular function of laser photocoagulation for diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 230:162–165

13.

Osborne NN, Barnett NL, Morris NJ, Huang FL (1992) The occurrence of three isoenzymes of protein kinase C (alpha, beta and gamma) in retinas of different species. Brain Res 570:161–166

14.

Rosner M, Solberg Y, Turetz J, Belkin M (1997) Neuroprotective therapy for argon-laser induced retinal injury. Exp Eye Res 65:485–495

15.

Shiba T, Inoguchi T, Sportsman JR, Heath WF, Bursell S, King GL (1993) Correlation of diacylglycerol level and protein kinase C activity in rat retina to retinal circulation. Am J Physiol 265:E783–E793

16.

Shimura M, Yasuda K, Nakazawa T, Kano T, Ohta S, Tamai M (2003) Quantifying alterations of macular thickness before and after panretinal photocoagulation in patients with severe diabetic retinopathy and good vision. Ophthalmology 110:2386–2394CrossRefPubMed

17.

Tassignon MJ, Stempels N, Nguyen-Legros J, De Wilde F, Brihaye M (1991) The effect of wavelength on glial fibrillary acidic protein immunoreactivity in laser-induced lesions in rabbit retina. Graefes Arch Clin Exp Ophthalmol 229:380–388

18.

The Diabetic Retinopathy Study Research Group (1976) Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol 81:383–396

19.

Wang A, Nomura M, Patan S, Ware JA (2002) Inhibition of protein kinase Calpha prevents endothelial cell migration and vascular tube formation in vitro and myocardial neovascularization in vivo. Circ Res 90:609–616

20.

Wellner M, Maasch C, Kupprion C, Lindschau C, Luft FC, Haller H (1999) The proliferative effect of vascular endothelial growth factor requires protein kinase C-alpha and protein kinase C-zeta. Arterioscler Thromb Vasc Biol 19:178–185

21.

Williams B, Gallacher B, Patel H, Orme C (1997) Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. Diabetes 46:1497–1503

22.

Wilson AS, Hobbs BG, Shen WY, Speed TP, Schmidt U, Begley CG, Rakoczy PE (2003) Argon laser photocoagulation-induced modification of gene expression in the retina. Invest Ophthalmol Vis Sci 44:1426–1434

23.

Wood JPM, McCord RJ, Osborne NN (1997) Retinal protein kinase C. Neurochem Int 30:119–136

24.

Xiao M, Sastry SM, Li ZY, Possin DE, Chang JH, Klock IB, Milam AH (1998) Effects of retinal laser photocoagulation on photoreceptor basic fibroblast growth factor and survival. Invest Ophthalmol Vis Sci 39:618–630

25.

Xiao M, McLeod D, Cranley J, Williams G, Boulton M (1999) Growth factor staining patterns in the pig retina following retinal laser photocoagulation. Br J Ophthalmol 83:728–736

Title: Protein kinase C expression in the rabbit retina after laser photocoagulation
Authors: Fredrik Ghosh
Karin Gjörloff
Publication date: 01-08-2005
Publisher: Springer-Verlag
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 8/2005
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-004-1112-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Protein kinase C expression in the rabbit retina after laser photocoagulation

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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