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. 2019 Mar 13;12(Suppl 2):48.
doi: 10.1186/s12920-019-0493-8.

Immunohistochemical localization of NGF, BDNF, and their receptors in a normal and AMD-like rat retina

Darya V Telegina  1 , Nataliya G Kolosova  2   3 , Oyuna S Kozhevnikova  4
Affiliations

Immunohistochemical localization of NGF, BDNF, and their receptors in a normal and AMD-like rat retina

Darya V Telegina et al. BMC Med Genomics. .

Abstract

Background: Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the molecular pathogenesis of AMD is poorly understood. A large body of evidence has corroborated the key role of neurotrophins in development, proliferation, differentiation, and survival of retinal cells. Neurotrophin deprivation has been proposed to contribute to retinal-cell death associated with neurodegenerative diseases. Little is known about the expression of the immature form of neurotrophins (proneurotrophins) and their mature form [e.g., nerve growth factor (proNGF and mNGF) and brain-derived neurotrophic factor (proBDNF and mBDNF)] in the retina during physiological aging and against the background of AMD. In addition, cell-specific localization of proteins NGF and BDNF in the retina during AMD development is not clear. Here, we evaluated contributions of the age-related alterations in the neurotrophin system to the development of AMD-like retinopathy in OXYS rats.

Methods: Male OXYS rats at preclinical (20 days), early (3 months), and late (18 months) stages of the disease and age-matched male Wistar rats (as controls) were used. We performed immunohistochemical localization of NGF, BDNF, and their receptors TrkA, TrkB, and p75NTR by fluorescence microscopy in retinal sections from OXYS and Wistar rats.

Results: We found increased NGF staining in Muller cells in 18-month-old OXYS rats (progressive stage of retinopathy). In contrast, we observed only subtle changes in the labeling of mature BDNF (mBDNF) and TrkB during the development of AMD-like retinopathy in OXYS rats. Using colocalization with vimentin and NeuN, we detected a difference in the cell type-specific localization of mBDNF between OXYS and Wistar rats. We showed that the mBDNF protein was located in Muller cells in OXYS rats, whereas in the Wistar retina, mBDNF immunoreactivity was detected in Muller cells and ganglion cells. During the development of AMD-like retinopathy, proBDNF dominated over mBDNF during increasing cell loss in the OXYS retina.

Conclusions: These data indicate that alterations in the balance of neurotrophic factors in the retina are involved in the development of AMD-like retinopathy in OXYS rats and confirm their participation in the pathogenesis of AMD in humans.

Keywords: Age-related macular degeneration; BDNF; NGF; OXYS rats; Retina; Retinopathy.

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Conflict of interest statement

Ethics approval and consent to participate

All the animal procedures and experimental protocols were approved by the Institutional Review Board of the Institute of Cytology and Genetics, according to The Guidelines for Manipulations of Experimental Animals.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
mNGF and TrkA expression in the rat retina during aging and development of AMD-like retinopathy. a Double-label immunofluorescent staining of mNGF (red) and TrkA (green) in the retina of OXYS and Wistar rats (n = 4) at various ages. b Double-label immunofluorescent staining of vimentin (red) and mNGF (green) in the retina of 18-month-old OXYS and Wistar rats. Vimentin expression increased at the advanced stage of AMD-like retinopathy. There was good colocalization of vimentin and mNGF in the OXYS retina. Nuclei were stained blue with DAPI. Abbreviations: GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer
Fig. 2
Fig. 2
mBDNF and TrkB expression in the rat retina during aging and development of AMD-like retinopathy. a Double-label immunofluorescent staining of mBDNF (green) and TrkB (red) in the retina of OXYS and Wistar rats (n = 4) at various ages. b Double-label immunofluorescent staining of NeuN (green) and mBDNF (red) in the retina of 3-month-old OXYS and Wistar rats. There was no mBDNF expression in the retinal ganglion cells of OXYS rats. c Double-label immunofluorescent staining of vimentin (red) and mBDNF (green) in the retina of 3-month-old OXYS and Wistar rats. There was mBDNF expression in the Muller glia of both OXYS and Wistar rat retinas. Nuclei were stained blue using DAPI. Abbreviations: GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer
Fig. 3
Fig. 3
proBDNF, mBDNF and p75NTR expression in the rat retina during aging and development of AMD-like retinopathy. a Double-label immunofluorescent staining of proBDNF (red) and p75NTR (green) in the retina of OXYS and Wistar rats (n = 4) at various ages. b Cryosections of OXYS and Wistar rat retinas were stained with antibodies against proBDNF (red) and mBDNF (green). proBDNF dominated over mBDNF in OXYS rats at all ages in comparison with Wistar rats. Abbreviations: GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer
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