title: Expression and localisation of BDNF, NT4 and TrkB in proliferative vitreoretinopathy.
abstract: Exogenous brain derived neurotrophic factor (BDNF) is known to rescue ganglion cell death after optic nerve injury. Its mechanism of action is believed to be indirect via glial cells in the retina. In this study we investigated the changes in expression and localisation of BDNF, neurotrophin-4 (NT4) and their common receptor (TrkB) in retinectomy sections of patients with proliferative vitreoretinopathy (PVR). Nine full-thickness retinectomy specimens obtained at retinal reattachment surgery for PVR were fixed in 4% paraformaldehyde immediately after excision and compared to similarly processed normal donor retinas (4 eyes). Agarose-embedded sections (100 microm thick) were double labelled for immunohistochemistry by confocal microscopy, with antibodies against BDNF, NT4, TrkB, rod opsin, glial fibrillary acidic protein (GFAP), cellular retinaldehyde binding protein (CRALBP) and Brn3. This study demonstrates expression of NT4 by ganglion cells and shows expression of BDNF and NT4 in the outer photoreceptor segments is downregulated during PVR, whilst NT4 is markedly upregulated throughout the retina during this condition. The findings here suggest that NT4 may play a neural protective role during the development of PVR. It also shows that upregulation of NT4 in PVR is localised to Müller glial cells, indicating either over-expression of this factor by Müller cells or that Müller cells internalise NT4 for trafficking across the retina. TrkB expression was not observed in PVR retina. The observations that Müller glia demonstrate upregulation of NT4 suggests that retinal injury may lead to activation of this neurotrophin by Müller cells as part of their neuroprotective functions.
authors.affiliation: Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK. ghazinouri@hotmail.com
authors.forename: Seyed M S
authors.initials: SM
authors.lastname: Ghazi-Nouri
authors.forename: James S
authors.initials: JS
authors.lastname: Ellis
authors.forename: Stephen
authors.initials: S
authors.lastname: Moss
authors.forename: G Astrid
authors.initials: GA
authors.lastname: Limb
authors.forename: David G
authors.initials: DG
authors.lastname: Charteris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005136:Eye Proteins; D009414:Nerve Growth Factors; D020813:Receptor, trkB; C073922:neurotrophin 4