April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Eye drops containing pigment epithelium-derived factor promotes retinal ganglion cell neuroprotection and axon regeneration
Author Affiliations & Notes
  • Zubair Ahmed
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Vasanthy Vigneswara
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Louise Deer
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Maryam Esmaeili
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Martin Berry
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Ann Logan
    Neurotrauma and Neurodegeneration, University of Birmingham, Birmingham, United Kingdom
  • Footnotes
    Commercial Relationships Zubair Ahmed, None; Vasanthy Vigneswara, None; Louise Deer, None; Maryam Esmaeili, None; Martin Berry, None; Ann Logan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5741. doi:
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    • Get Citation

      Zubair Ahmed, Vasanthy Vigneswara, Louise Deer, Maryam Esmaeili, Martin Berry, Ann Logan; Eye drops containing pigment epithelium-derived factor promotes retinal ganglion cell neuroprotection and axon regeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5741.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

We recently showed that pigment epithelium-derived factor (PEDF), a 50kDa glycoprotein, is retinal ganglion cell (RGC) neurotrophic and axogenic. In this study, we tested the therapeutic utility of an eye drop formulation of PEDF to protect RGC from death and promote their axon regeneration after an optic nerve crush.

 
Methods
 

Bilateral optic nerve crushes were performed in rats followed by daily eye drops for a period of 21 days. RGC death was assessed by Fluorgold injection into the optic nerve proximal to the crush site. The number of Flurogold labelled RGC was quantified in retinal using image analysis. GAP43 was used to assess axon regeneration at various distances from the lesion. Western blot and ELISA of retinal homogenates were used to detect the titres of PEDF reaching the vitreous and the retina after eye drops.

 
Results
 

Eye drop delivery led to the accumulation of significant titres of PEDF compared to intact eyes, detected by western blot of retinal lysates after 0.5hr with levels decreasing over time. After eye drops containing 5μg of PEDF, ELISA of vitreous samples and retinal lysates detected 1.4 and 0.6μg of PEDF after 0.5hr, 1.35 and 0.8 μg after 4hr, dropping to 0.43 and 0.35μg after 24hr, respectively (Fig. 1). Daily eye drops protected 65% of RGC from axotomy-induced death and promoted 5-fold more RGC axon regeneration than intravitreal injection of the same concentration of PEDF every 7 days (Fig. 2).

 
Conclusions
 

Our results suggest that eye drops of PEDF are neuroprotective and RGC axon regenerative and may be a useful therapeutic in the fight against eye disease where RGC death and axon damage are key features of disease.

 
 
Figure 1: (A) Western blots of vitreous and retina after 0.5, 4 and 24hr. After eye drop delivery of 5μg PEDF and bands were quantified by (B) densitometry, while (C) ELISA detected 1.4 and 0.6μg in vitreous and retinal homogenates.
 
Figure 1: (A) Western blots of vitreous and retina after 0.5, 4 and 24hr. After eye drop delivery of 5μg PEDF and bands were quantified by (B) densitometry, while (C) ELISA detected 1.4 and 0.6μg in vitreous and retinal homogenates.
 
 
Figure 2. GAP43 staining demonstrated few surviving GAP43+ axons after (A) optic nerve crush with evidence of significant regeneration after (B-C) ONC+PEDF ivit treatment. (E) The greatest number of axons were localised in ONC+PEDF eye drop groups.
 
Figure 2. GAP43 staining demonstrated few surviving GAP43+ axons after (A) optic nerve crush with evidence of significant regeneration after (B-C) ONC+PEDF ivit treatment. (E) The greatest number of axons were localised in ONC+PEDF eye drop groups.
 
Keywords: 531 ganglion cells • 615 neuroprotection • 687 regeneration  
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