Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: A quantitative in vivo study

Parrilla–Reverter, G.; Agudo, Marta; Sobrado‐Calvo, Paloma; Salinas‐Navarro, Manuel; Villegas‐Pérez, María Paz; Vidal‐Sanz, Manuel

doi:10.1016/j.exer.2009.02.015

Cited by 137 publications

(118 citation statements)

References 54 publications

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“…Our group has shown that a single intravitreal injection of neurotrophin 4 (NT-4), ciliary neurotrophic factor (CNTF), or brain derived neurotrophic factor (BDNF) at the moment of the injury delays IONC-induced RGC death (Parrilla-Reverter et al, 2009b). At 7dpl all of them prevent almost completely the loss of RGCs.…”

Section: Therapies To Increase the Resistance Of The Injured Neuronsmentioning

confidence: 99%

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

Agudo‐Barriuso¹,

Nadal-Nicolás²,

Parrilla–Reverter³

et al. 2011

The Mystery of Glaucoma

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Section: Therapies To Increase the Resistance Of The Injured Neuronsmentioning

confidence: 99%

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

Agudo‐Barriuso¹,

Nadal-Nicolás²,

Parrilla–Reverter³

et al. 2011

The Mystery of Glaucoma

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“…PEDF may, thus, function both directly and indirectly in the retina as a Müller cellderived RGC axogenic factor after ON transection and also protect RGC by suppressing caspase activity, preserving glutamine synthetase levels, preventing the accumulation of reactive oxygen species and counteracting the detrimental effects of gliosis. [71][72][73][74][83][84][85] Other commonly used RGC neuroprotective factors include BDNF, GDNF, NT-3, NT-4/5, TrkB gene transfer, as well as caspase inhibitors. 45,53,59,[75][76][77][78][79][80][83][84][85][86] Although we showed that BDNF administration in our ONC model supported nearly 100% survival of RGC at 7 days, 53 long-term studies with BDNF peptide or gene transfer showed that BDNF supported approximately 60% of RGC survival at 2 weeks after ON transection.…”

mentioning

confidence: 99%

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

Vigneswara¹,

Berry²,

Logan³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Vigneswara V, Berry M, Logan A, Ahmed Z. Pigment epithelium-derived factor is retinal ganglion cell neuroprotective and axogenic after optic nerve crush injury. Invest Ophthalmol Vis Sci. 2013;54: 262454: -263354: . DOI: 10.1167 PURPOSE. To investigate neuroprotective and axogenic properties of pigment epitheliumderived factor (PEDF) in retinal ganglion cells (RGC) in vitro and in vivo.METHODS. Adult rat retinal cultures were treated with combinations of PBS and PEDF with or without a cell permeable analogue of cAMP, and RGC survival and neurite lengths quantified. The optic nerves of anesthetised rats were also crushed intraorbitally to transect all RGC axons followed by intravitreal injections of either PBS, PEDF, or cAMPþPEDF every 7 days. RGC were back filled with FluoroGold to quantify RGC survival and longitudinal optic nerve sections were stained with GAP43 antibodies to detect regenerating RGC axons.RESULTS. An optimal dose of 2.5 3 10 À5 lg/lL, promoted 65% more RGC survival than controls in vitro, increasing by 4.4-and 5-fold the number of RGC with neurites and the mean neurite length, respectively. Addition of cAMP with or without PEDF did not potentiate RGC survival or the mean number of RGC with neurites, but enhanced RGC neurite length by 1.4-fold, compared with PEDF alone. After optic nerve crush (ONC), PEDF protected RGC from apoptosis and increased the numbers of regenerating RGC axons in the optic nerve by 4.6-and 3.4-fold, respectively when compared with controls. cAMP did not enhance PEDF-induced RGC neuroprotection, but potentiated its neuroregenerative effects by 2-to 3-fold, increasing the number of RGC axons regenerating at 500 and 1000 lm from the lesions site.CONCLUSIONS. This study is the first to demonstrate that PEDF enhances both RGC survival and axon regeneration in vitro and in vivo.Keywords: PEDF, retinal ganglion cells, neuroprotection, axon regeneration, optic nerve R etinal ganglion cells (RGC) rapidly die after axotomy, but are protected by combinatorial treatments with neurotrophic factors (NTF), including brain-derived NTF (BDNF), neurotrophin-3/4 (NT-3/4), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic (GDNF), and basic fibroblast growth factor (FGF2). 1-7 NTF combinations also activate intrinsic axon growth signalling pathways that initiate RGC axon regeneration.1-7 Pigment epithelium-derived factor (PEDF) is a 50 kDa NTF glycoprotein belonging to the serpin superfamily, that protects a wide range of central nervous system (CNS) neurons. [8][9][10][11][12][13][14][15] Although first isolated from fetal human retinal pigment (choroid) epithelial cells, like many other NTF, PEDF is expressed in a wide variety of tissues including brain, spinal cord, skeletal muscle, heart, endothelial cells, and osteoblasts. [16][17][18][19][20] PEDF has an array of unique properties including neuroprotective, anti-angiogenic, antiinflammatory, anti-oxidative, and antitumorigenic activities. [21][22][23][24][25][26][27] PEDF is a multifaceted NTF that ...

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“…The notion of a neuroprotectant role for BDNF in POAG derives from the ob servation that death of retinal ganglion cells (RGCs) induced by axotomy of optic nerves is rescued by intravitreal BDNF administration in rodents [42,43] and cats [44]. RGCs and optic nerve fibres express TrkB in the adult retina [4548] and it is known that BDNF is transported by both antero grade and retrograde axonal transport in these cells [49][50][51][52][53].…”

Section: Bdnf and Poagmentioning

confidence: 99%

Role of Brain-Derived Neurotrophic Factor for the Treatment of Glaucoma and Retinitis Pigmentosa

Spaccapelo¹

2016

MOJT

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Primary open-angle glaucoma (POAG) is the most common form of glau¬co¬ma, representing up to 90% of cases. POAG is described as a multifactorial optic neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve fibres. The cause for the elevated is generally IOP accepted to be decreased facility of aqueous outflow through the trabecular meshwork. Retinitis pigmentosa (RP) is a group of relatively rare, inherited disorders characterized by progressive peripheral vision loss and night vision difficulties (nyctalopia) that can lead to central vision loss due to the degeneration of the rod photoreceptor cells in the retina. RP manifests initial symptoms in-dependent of age; thus, RP diagnosis occurs anywhere from early infancy to late adulthood. Brain-derived neurotrophic factor (BDNF) is a 14 kDa protein belonging to the neurotrophin family of growth factors. BDNF has trophic functions in the hippocampus, cortex, and basal forebrain as well as the retina, motor neurons, the kidneys, saliva, and the prostate. The notion that BDNF may have a role in treating the neurodegenerative aspects of POAG is underpinned by convincing preclinical evidence in animal models of glaucoma that BDNF administered intravitreously can, at least in part, rescue retinal ganglion cells (RGCs) under conditions such as those induced by increased intraocular pressure(IOP). Overall, and despite a mechanistically sound rationale, the pharmacokinetic challenges indicate that instilled BDNF topical administration is associated with higher than normal risks, likely explaining the emphasis on alternative approaches (such as synthetic small molecule BDNF analogues or gene therapy approaches) in the last decade. Moreover, the high BDNF doses required to drive efficacy (and low target tissue penetration) also raise concerns over promotion of tumour growth resulting from BDNF taken up from non-retinal tissues. In conclusion, even if preliminary evidences are available, further studies are necessary in order to clarify the role of BDNF for the treatment of glaucoma and retinitis pigmentosa. Keywords:

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Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: A quantitative in vivo study

Cited by 137 publications

References 54 publications

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

Role of Brain-Derived Neurotrophic Factor for the Treatment of Glaucoma and Retinitis Pigmentosa

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