Biology Reference
In-Depth Information
Chapter 16
Photoreceptor Degeneration in Mice: Adeno-Associated Viral
Vector-Mediated Delivery of Erythropoietin
Pasqualina Colella and Alberto Auricchio
Abstract
The exogenous delivery of erythropoietin (EPO) and EPO derivatives (EPO-Ds) represents a valuable
strategy to protect the retina from degeneration. In this chapter we describe a method to deliver EPO and
the EPO derivative S100E in the light-damage model of induced retinal degeneration using adeno-
associated viral (AAV) vectors and to evaluate the functional and morphological protection of the retina
from light damage.
Key words
Retina, Photoreceptor degeneration, Adeno-associated viral vectors, Erythropoietin
derivatives, Light damage
1
Introduction
Inherited retinal degenerations (IRDs) are common untreatable
conditions leading to blindness that include retinitis pigmentosa
(RP) (
1
), Leber congenital amaurosis (LCA) (
2
), and cone-rod dys-
trophies (
3
). IRDs are characterized by high genetic heterogeneity.
Nonetheless, they show a common phenotype consisting in photo-
receptor (PR) dysfunction and progressive PR cell loss (
4
). Based
on this, the delivery of neurotrophic/antiapoptotic genes, proteins,
or compounds may represent a valuable strategy to either inhibit/
slow down PR cell death or to sustain PR function and/or survival
independently of the mutated gene (
5-8
). Notably, many studies
have reported that EPO exerts a protective function on retinal pho-
toreceptors (PRs) (
9-12
), ganglion cells (GCs) (
13-17
), and on
the retinal pigment epithelium (RPE) (
18-20
) (Fig.
1
). The deliv-
ery of EPO through viral vectors allows sustained and/or regulat-
able expression (
21, 22
) and would be advantageous to avoid
repeated systemic or intraocular administrations that would be
required to treat chronic and progressive diseases like IRDs. Vectors
derived from the adeno-associated virus (AAV) are the most efficient
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