Purchase this article with an account.
Manuel Marcel Hermann, Andrea Luise Schindler, Sascha Fauser; Immunohistochemical localization of membrane attack complex and C5a receptor in the human retina . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3778.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Genetic studies have found strong associations between age-related macular degeneration (AMD) and variants of complement pathway-associated genes. The regulation of the complement cascade seems to be critical in the pathogenesis of AMD. We here aimed at localizing membrane attack complex (MAC) and C5a receptor (CD88) in the human retina of eyes affected with AMD and normal eyes. MAC forms the terminal complex of the complement cascades which leads to cell lysis. C5a has chemotactic and anaphylatoxic properties, is essential for the innate immunity, but has also been linked to adaptive immunity.
A total of 45 tissue specimens of 28 donors was obtained from the Eye Bank of the Center of Ophthalmology, University of Cologne, Germany. Donor age ranged between 19 and 78 (mean 57) years. Prior to fixation, retinal specimens were graded using the international classification and grading system for age-related maculopathy and AMD.<br /> After fixation and paraffin embedding immunohistochemistry was performed using antibodies directed against (i) MAC (polyclonal rabbit anti human C5b-9), (ii) C5a receptor (monoclonal mouse anti human CD88, clone S5/1), and (iii) isotype controls, all followed by peroxidase labelling and chromogenic detection.
Eleven specimens obtained from 9 donors were graded as early AMD and 34 specimens from 24 donors as controls. For all eyes C5a receptor staining was found in the apical part of the outer plexiform layer, and -less intense- in the inner plexiform layer and nerve fiber layer. MAC staining was detected in intercapillary pillars of choroid and in 24 cases staining in the RPE and in all drusen. We found no differences in intensity or patterns between AMD and controls when staining for C5a receptor or MAC.
The sharp and continuous staining of C5a receptor in the outer plexiform layer implies specific complement activity or a particular regulation zone at this level of the retina. The presence of MAC at the level of Bruch's membrane, adjacent intercapillary pillars of the choroid and the retinal pigment epithelium underpins the importance of this site in the control of complement activity. Hence, unbalanced regulation of complement activity might represent a key factor ultimately leading to AMD.
This PDF is available to Subscribers Only