NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study

Falsini, Benedetto; Iarossi, Giancarlo; Chiaretti, Antonio; Ruggiero, Antonio; Manni, Luigi; Galli‐Resta, Lucia; Corbo, Giovanni; Abed, Edoardo

doi:10.1186/s12967-015-0750-3

Cited by 47 publications

(25 citation statements)

References 27 publications

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“…The pathological process of RP is influenced by a spectrum of molecular, cellular, and tissue-level factors (Lemos Reis et al, 2015). In view of the enormous heterogeneity implied in etiology, RP patients always have highly variable onset points, progressive dynamics, and prognosis outcomes (Cai et al, 2014;Falsini et al, 2016). These variations make the accurate diagnosis extremely challenging.…”

Section: Introductionmentioning

confidence: 99%

Intravitreal Delivery of Melatonin Is Protective Against the Photoreceptor Loss in Mice: A Potential Therapeutic Strategy for Degenerative Retinopathy

Tian

Yao

et al. 2020

Front. Pharmacol.

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Melatonin is a circadian hormone with potent cytoprotective effects. Retinitis pigmentosa (RP) comprises a heterogeneous group of inherent retinopathies that characterized by the photoreceptor death in bilateral eyes. The N-methyl-N-nitrosourea (MNU) administered mouse is a type of chemically induced RP model with rapid progressive rate. We intend to study the melatonin mediated effects on the MNU administered mice. Melatonin was delivered into the vitreous body of the MNU administered mice. Subsequently, the melatonin treated mice were subjected to histological analysis, optokinetic behavior tests, spectral-domain optical coherence tomography (SD-OCT), and electroretinogram (ERG) examination. Multi-electrodes array (MEA) was used to analyze the status of visual signal transmission within retinal circuits. Biochemical analysis was performed to quantify the expression levels of antioxidative enzymes, oxidative stress markers, and apoptotic factors in the retinas. The intravitreal injection of melatonin ameliorated effectively the MNU induced photoreceptor degeneration. Melatonin therapy mitigated the spontaneous firing response, and preserved the basic configurations of visual signal pathway in MNU administered mice. MEA is effective to evaluate the pharmacological effects on retina. Of note, the cone photoreceptors in degenerative retinas were rescued efficiently by melatonin therapy. Melatonin afforded these protective effects by modulating the apoptotic cascades and alleviating the oxidative stress. These findings suggest that melatonin could act as an alternative treatment for degenerative retinopathy. Melatonin Frontiers in Pharmacology | www.frontiersin.org

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Section: Introductionmentioning

confidence: 99%

Intravitreal Delivery of Melatonin Is Protective Against the Photoreceptor Loss in Mice: A Potential Therapeutic Strategy for Degenerative Retinopathy

Tian

Yao

et al. 2020

Front. Pharmacol.

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“…Some of these patients demonstrated an increase in visual acuity, a temporary enlargement of the VF and an improvement in macular focal ERG findings. This study suggested that the application of NGF eye-drop is safe and efficient in at least some of the RP patients [25].…”

Section: Discussionmentioning

confidence: 65%

Subtenon Injection of Autologous Platelet-Rich Plasma in Retinitis Pigmentosa: Is It a New Therapeutic Option?

Kahraman¹,

Öner²

2020

OJOph

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Purpose: Growth factors (GFs) and neurotrophins can decelerate retinal degeneration. This study aimed to investigate the safety, efficacy and durability of subtenon injections of autologous platelet-rich plasma (aPRP) which is a rich source of GFs in retinitis pigmentosa (RP) patients. Methods: 154 eyes of 77 RP patients with various degrees of narrowed visual field were investigated in this study. Each patient received three injections with 4-week intervals and followed for at least 12 months. The examinations and the tests were obtained before the injection, 1 month after the third injection and every 3 months during the study. The primary aim was to evaluate the effects of aPRP on visual acuity (VA) and visual functions, the second aim was to estimate the duration of the therapy effect and the need for additional aPRP injection. Results: Median age of the 77 RP patients was 35.2 ± 13.9 years. All of the eyes received 3 monthly bilateral subtenon aPRP injections. Of these patients 26 received an additional one, 12 received additional two and 1 patient received additional 3 injections with 3-month interval. There were no significant ocular or systemic side effects. The mean baseline VA was 0.22 ± 0.18 Snellen lines. It improved to 0.31 ± 0.19 following three aPRP injections, which was statistically significant. At the end of the study period, the mean VA was 0.27 ± 0.22 Snellen lines. Conclusion: The subtenon injection of aPRP might be an effective therapy and might have a positive influence in the preservation of visual functions and visual acuity of RP patients.

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“…Topical administration of NGF therefore has been attempted and demonstrated to be effective experimentally 25,26,40,42 . Topical NGF is already approved for treatment in humans with neurotrophic keratitis 44 , and is safe, well tolerated and effective in patients 26,[44][45][46][47] . It has not been used for any other clinical ocular indication.…”

Section: Resultsmentioning

confidence: 99%

Topical recombinant human Nerve growth factor (rh-NGF) is neuroprotective to retinal ganglion cells by targeting secondary degeneration

Guo

Davis

Ravindran

et al. 2020

Sci Rep

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Optic neuropathy is a major cause of irreversible blindness worldwide, and no effective treatment is currently available. Secondary degeneration is believed to be the major contributor to retinal ganglion cell (RGc) death, the endpoint of optic neuropathy. partial optic nerve transection (pont) is an established model of optic neuropathy. Although the mechanisms of primary and secondary degeneration have been delineated in this model, until now how this is influenced by therapy is not well-understood. in this article, we describe a clinically translatable topical, neuroprotective treatment (recombinant human nerve growth factor, rh-nGf) predominantly targeting secondary degeneration in a pONT rat model. Topical application of rh-NGF twice daily for 3 weeks significantly improves RGc survival as shown by reduced RGc apoptosis in vivo and increased RGc population in the inferior retina, which is predominantly affected in this model by secondary degeneration. Topical rh-NGF also promotes greater axonal survival and inhibits astrocyte activity in the optic nerve. collectively, these results suggest that topical rh-NGF exhibits neuroprotective effects on retinal neurons via influencing secondary degeneration process. As topical rh-nGf is already involved in early clinical trials, this highlights its potential in multiple indications in patients, including those affected by glaucomatous optic neuropathy. Secondary degeneration occurs commonly in the central (CNS) and peripheral (PNS) nervous systems, where injury from initial lesions can lead to widespread damage to neurons far beyond the primary injury site 1. The second phase of injury is thought to be caused by the accumulation of noxious factors such as oxidative radicals, glutamate and calcium release from primarily damaged cells and peripheral immune cell activation 2-5. Secondary neurodegeneration is believed to be the major contributor to neuronal death in CNS injuries including those affecting the spinal cord 1,6 and in optic neuropathies, such as glaucoma, ischaemic optic neuropathy, and Leber's hereditary optic neuropathy 7-9. Optic neuropathy describes a collection of disorders characterised by damage to the optic nerve and loss of retinal ganglion cells (RGCs) due to any cause, including glaucoma, ischaemia, trauma and genetic predisposition 10,11. Of these, glaucoma represents the leading cause of global irreversible blindness, affecting over 60.5 million people, a figure set to double by 2040 9,12. Currently, intraocular pressure (IOP) presents the only therapeutically modifiable risk factor for glaucoma 13 ; however, patients with well-controlled IOP can still lose vision (disease progression), necessitating the development of novel, non-IOP-dependent treatment strategies for this condition 14. Neuroprotective therapies are increasingly recognized as a promising approach to slow or prevent optic neuropathy associated RGC loss 15,16 , and the use of new endpoints and biomarkers, such as DARC

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NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study

Cited by 47 publications

References 27 publications

Intravitreal Delivery of Melatonin Is Protective Against the Photoreceptor Loss in Mice: A Potential Therapeutic Strategy for Degenerative Retinopathy

Intravitreal Delivery of Melatonin Is Protective Against the Photoreceptor Loss in Mice: A Potential Therapeutic Strategy for Degenerative Retinopathy

Subtenon Injection of Autologous Platelet-Rich Plasma in Retinitis Pigmentosa: Is It a New Therapeutic Option?

Topical recombinant human Nerve growth factor (rh-NGF) is neuroprotective to retinal ganglion cells by targeting secondary degeneration

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