Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration.

Vigneswara, Vasanthy, Esmaeili, Maryam, Deer, Louise, Berry, Martin, Logan, Ann and Ahmed, Zubair 2015. Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration. Molecular and Cellular Neuroscience 68 , pp. 212-221. 10.1016/j.mcn.2015.08.001

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Abstract

Axotomised retinal ganglion cells (RGCs) die rapidly by apoptosis and fail to regenerate because of the limited availability of neurotrophic factors and a lack of axogenic stimuli. However, we have recently showed that pigment epithelium-derived factor (PEDF) promotes RGC survival and axon regeneration after optic nerve crush injury. PEDF has multiple fragments of the native peptide that are neuroprotective, anti-angiogenic and anti-inflammatory. Here we investigated the neuroprotective and axogenic properties of a fragment of PEDF, PEDF-34, in retinal neurons in vitro and when delivered by intravitreal injection and eye drops in vivo. We found that PEDF-34 was 43% more neuroprotective and 52% more neuritogenic than PEDF-44 in vitro. Moreover, in vivo, intravitreal delivery of 1.88nM PEDF-34 was 71% RGC neuroprotective at 21days after optic nerve crush compared to intact controls, whilst daily eye drops containing 1.88nM PEDF-34 promoted 87% RGC survival. After topical eye drop delivery, PEDF-34 was detected in the vitreous body within 30min and attained physiologically relevant concentrations in the retina by 4h peaking at 1.4±0.05nM by 14days. In eye drop- compared to intravitreal-treated PEDF-34 animals, 55% more RGC axons regenerated 250μm beyond the optic nerve lesion. We conclude that daily topical eye drop application of PEDF-34 is superior to weekly intravitreal injections in promoting RGC survival and axon regeneration through both direct effects on retinal neurons and indirect effects on other retinal cells.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Optometry and Vision Sciences
Publisher:	Elsevier
ISSN:	1044-7431
Date of First Compliant Deposit:	4 July 2025
Date of Acceptance:	3 August 2015
Last Modified:	04 Jul 2025 13:00
URI:	https://orca.cardiff.ac.uk/id/eprint/179502

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