Affiliations: [a] Institute of Biochemistry and Cell Biology, Medical Faculty, University of Magdeburg, Magdeburg, Germany
| [b] Department of Anesthesiology, Medical Faculty, University of Magdeburg, Magdeburg, Germany
Correspondence:
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Corresponding author: Gerburg Keilhoff, Institute of Biochemistry and Cell Biology, Medical Faculty, University of Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. Tel.: +49 396 67 14368; Fax: +49 396 67 14365; E-mail: [email protected].
Abstract: Background:Stroke-related loss of vision is one of the residual impairments, restricting the quality of life. However, studies of the ocular manifestations of asphyxia cardiac arrest/resuscitation (ACA/R) have reported very heterogeneous results. Objective:We aimed to evaluate the ACA/R-induced degeneration pattern of the different retinal cell populations in rats using different immuno-histological stainings. Methods:The staining pattern of toluidine blue and the ganglion cell markers β-III-tubulin and NeuN; the calcium-binding protein parvalbumin, indicating ganglion, amacrine, and horizontal cells; calretinin D28k, indicating ganglion and amacrine cells; calbindin, indicating horizontal cells; Chx 10, indicating cone bipolar cells; PKCα, indicating ON-type rod bipolar cells; arrestin, indicating cones; and rhodopsin, a marker of rods, as well as the glial cell markers GFAP (indicating astroglia and Müller cells) and IBA1 (indicating microglia), were evaluated after survival times of 7 and 21 days in an ACA/R rat model. Moreover, quantitative morphological analysis of the optic nerve was performed. The ACA/R specimens were compared with those from sham-operated and completely naïve rats. Results:ACA/R-induced effects were: (i) a significant reduction of retinal thickness after long-term survival; (ii) ganglion cell degeneration, including their fiber network in the inner plexiform layer; (iii) degeneration of amacrine and cone bipolar cells; (iv) degeneration of cone photoreceptors; (v) enhanced resistance to ACA/R by rod photoreceptors, ON-type rod bipolar and horizontal cells, possibly caused by the strong upregulation of the calcium-binding proteins calretinin, parvalbumin, and calbindin, counteracting the detrimental calcium overload; (vi) significant activation of Müller cells as further element of retinal anti-stress self-defense mechanisms; and (vii) morphological alterations of the optic nerve in form of deformed fibers. Conclusions:Regardless of the many defects, the surviving neuronal structures seemed to be able to maintain retinal functionality, which can be additionally improved by regenerative processes true to the “use it or lose it” dogma.
