Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death

Kido, Noriaki; Tanihara, Hidenobu; Honjo, Megumi; Inatani, Masaru; Tatsuno, Tohru; Nakayama, Chikao; Honda, Yoshio

doi:10.1016/s0006-8993(00)02887-0

Cited by 65 publications

(35 citation statements)

References 24 publications

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“…A null mutation of the bdnf gene in mice resulted in atrophy of dopaminergic amacrine cells (15). In addition, BDNF was reported to prevent the death of dopaminergic neurons in the substantia nigra (33) and retinal amacrine cells in vitro (13) and in vivo (14). Immunohistochemical analysis showed that BDNF protein levels in both RGCs and Mü ller cells were reduced in diabetic retinas (Fig.…”

Section: Discussionmentioning

confidence: 94%

“…Among them, brainderived neurotrophic factor (BDNF) is expressed in retinal ganglion cells (RGCs) and Mü ller glia in the retina (11) and is important for the survival of RGCs (12). It has also been reported (13,14) to prevent amacrine cell death. In addition to being a survival factor, BDNF acts as a synaptic modulator and has been shown (15) to cause hypertrophy of the retinal dopaminergic system in the rat retina.…”

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confidence: 99%

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Involvement of Brain-Derived Neurotrophic Factor in Early Retinal Neuropathy of Streptozotocin-Induced Diabetes in Rats

et al. 2004

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Although neurotrophins have been assessed as candidate therapeutic agents for neural complications of diabetes, their involvement in diabetic retinopathy has not been fully characterized. We found that the protein and mRNA levels of brain-derived neurotrophic factor (BDNF) in streptozotocin-induced diabetic rat retinas were reduced to 49% (P < 0.005) and 74% (P < 0.05), respectively, of those of normal control animals. In addition, dopaminergic amacrine cells appeared to be degenerating in the diabetic rat retinas, as revealed by tyrosine hydroxylase (TH) immunoreactivity. Overall TH protein levels in the retina were decreased to onehalf that of controls (P < 0.01), reflecting reductions in the density of dopaminergic amacrine cells and the intensity of TH immunoreactivity within them. To confirm the neuropathological implications of BDNF reduction, we administered BDNF protein into the vitreous cavities of diabetic rats. Intraocular administration of BDNF rescued dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of TH expression, demonstrating its therapeutic potential. These findings suggest that the early retinal neuropathy of diabetes involves the reduced expression of BDNF and can be ameliorated by an exogenous supply of this neurotrophin.

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Section: Discussionmentioning

confidence: 94%

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confidence: 99%

Involvement of Brain-Derived Neurotrophic Factor in Early Retinal Neuropathy of Streptozotocin-Induced Diabetes in Rats

et al. 2004

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“…93,94 This model has been reported to be performed in rats, 92,95,96 cats, 97 mice, 98 and hamsters. 99 Apart from this, other animal models, used to establish the BDNF activity in the retina, include light damage, 100 elevated intraocular pressure, 101 potassium cyanide-induced retinal damage, 102 N-methyl-d-aspartate (NMDA) excitotoxicity, 103 optic nerve trauma, 97 anterior ischemic optic neuropathy, 104 exploiting the dystrophic royal college of surgeons (RCS) rats strain 105 and investigation of the normal retina development in young rats. 106 Direct BDNF delivery to the posterior eye segment Pure …”

Section: Bdnf As a Therapeutic Option For Blindnessmentioning

confidence: 99%

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Khalin¹,

Alyautdin²,

Kocherga³

et al. 2015

IJN

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Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration.

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“…Although the precise combination of peptide factors needed for survival of healthy ganglion cells has not yet been delineated, a large body of work has established that administration of various trophic factors can delay and even partially prevent gangion cell death after not only optic nerve injury, 70 but also following high-pressure ischaemia, 71,72 or injection of NMDA. 73 Many trophic factors, including brain-derived neurotropic factor, ciliary neurotropic factor, glial cell line-derived neurotropic factor, neurotrophins 3 and 4, fibroblast growth factor-2, and nerve growth factor have been shown to exert beneficial effects on ganglion cell survival after injury, but none of these compounds have been able to stimulate significant neuronal regeneration after optic nerve injury. It will be interesting to determine the influence of these peptide factors on the rate and extent of optic nerve and ganglion cell injury after permanent occlusion of the carotid arteries, since the injury is vascular rather than mechanical in nature.…”

Section: Role Of Peptide Factors In the Protection Of Injured Gangliomentioning

confidence: 99%

Optic nerve and neuroprotection strategies

Osborne

Chidlow

Layton

et al. 2004

Eye

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Background Experimental studies have yielded a wealth of information related to the mechanism of ganglion cell death following injury either to the mylinated ganglion cell axon or to the ganglion cell body. However, no suitable animal models exist where injury can be directed to the optic nerve head region, particularly the unmylinated ganglion cell axons. The process of relating the data from the various animal models to many different types of optic neuropathies in man must, therefore, be cautious. Results Extensive studies on the isolated optic nerve have yielded valuable information on the way white matter is affected by ischaemia and how certain types of compounds can attenuate the process. Moreover, there are now persuasive data on how ganglion cell survival is affected when the ocular blood flow is reduced in various animal models. As a consequence, the molecular mechanisms involved in ganglion cell death are fairly well understood and various pharmacological agents have been shown to blunt the process when delivered before or shortly after the insult. Conclusions A battery of agents now exist that can blunt animal ganglion cell death irrespective of whether the insult was to the ganglion cell body or the mylinated axon. Whether this information can be applied for use in patients remains a matter of debate, and major obstacles need to be overcome before the laboratory studies may be applied clinically. These include the delivery of the pharmacological agents to the site of ganglion cell injury and side effects to the patients. Moreover, it is necessary to establish whether effective neuroprotection is only possible when the drug is administered at a defined time after injury to the ganglion cells. This information is essential in order to pursue the idea that a neuroprotective strategy can be applied to a disease like glaucoma, where

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Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death

Cited by 65 publications

References 24 publications

Involvement of Brain-Derived Neurotrophic Factor in Early Retinal Neuropathy of Streptozotocin-Induced Diabetes in Rats

Involvement of Brain-Derived Neurotrophic Factor in Early Retinal Neuropathy of Streptozotocin-Induced Diabetes in Rats

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Optic nerve and neuroprotection strategies

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