PEDF deficiency increases the susceptibility of rd10 mice to retinal degeneration. (September 2020)

• Record Type: Journal Article
• Authors: Dixit, Shivani; Polato, Federica; Samardzija, Marijana; Abu-Asab, Mones; Grimm, Christian; Crawford, Susan E.; Becerra, S. Patricia
• Is Part Of: Experimental eye research. Volume 198(2020)
• Publication Date: 2020-09
• Subjects: PEDF -- Serpinf1 -- Pigment epithelium-derived factor -- Retinal degeneration -- rd10 -- NaIO3; PEDF pigment epithelium-derived factor -- retinal pigment epithelium (RPE) -- interphotoreceptor matrix (IPM) -- osteogenesis imperfecta (OI) -- sodium iodate (NaIO3) -- phosphodiesterase 6B (Pde6b) -- wild type (WT) -- oculus sinister or left eye (OS) -- oculus dextrus or right eye (OD) -- hematoxylin and eosin (H&E) -- inner nuclear layer (INL) -- ganglion cell layer (GCL) -- outer nuclear layer (ONL) -- Transmission electron microscopy (TEM); Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.108121
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: The SERPINF1 gene encodes pigment epithelium-derived factor (PEDF), a member of the serpin superfamily with neurotrophic and antiangiogenic properties in the retina. We hypothesized that absence of PEDF would lead to increased stress-associated retinal degeneration in Serpinf1 null mice. Accordingly, using a Serpinf1 null mouse model, we investigated the impact of PEDF absence on retinal morphology, and susceptibility to induced and inherited retinal degeneration. We studied the pattern of Serpinf1 expression in the mouse retina layers. PEDF protein was detected by western blotting. Transmission electron microscopy was performed on mouse retina. Serpinf1 null mice and wild type littermates were injected with NaIO3 (30 mg/kg body weight) intraperitonially. At post-injection day 1, 3, 4, 6 and 8 mice were euthanized, and eyes were enucleated. Serpinf1 null and rd10 double mutant mice were generated and their eyes enucleated at different time points from post-natal day 15 to post-natal day 28. Enucleated eyes were processed for hematoxylin and eosin staining and histopathological evaluations. We found that Serpinf1 was expressed in the retinal pigment epithelium, in the inner nuclear layer and in the ganglion cell layer, but undetectable in the outer nuclear layer of wild type mice. Plasma PEDF protein levels were undetectable in Serpinf1 null animals. RPE atrophy and retinal thinning were observed in NaIO3 -treated wild type mice that progressed with time post-injection. NaIO3 -treated Serpinf1 null mice showed comparatively better retinal morphology than wild type mice at day 4 post-injection. However, the absence of PEDF in Serpinf1 null x rd10 mice increased the susceptibility to retinal degeneration relative to that of rd10 mice. We concluded that histopathological evaluation of retinas lacking PEDF showed that removal of the Serpinf1 gene may activate PEDF-independent compensatory mechanisms to protect the retina against oxidative stress, while it increases the susceptibility to degenerate the retina in inherited retinal degeneration models. Highlights: The SERPINF1 gene encodes the pigment epithelium-derived factor (PEDF) polypeptide. Serpinf1 was expressed in RPE, INL and RGC, but undetected in photoreceptors. Retinas of Serpinf1 null and WT mice had identical ERGs and similar structure. NaIO3 administration impacted the RPE of WT more than the Serpinf1 null RPE. Lack of PEDF influenced the magnitude of photoreceptor degeneration in rd10 mice.