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Maria Frasson, Serge Picaud, Thierry Léveillard, Manuel Simonutti, Saddek Mohand–Said, Henri Dreyfus, David Hicks, José Sahel; Glial Cell Line–Derived Neurotrophic Factor Induces Histologic and Functional Protection of Rod Photoreceptors in the rd/rd Mouse. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2724-2734.
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purpose. To evaluate the neuroprotective potential of glial cell line–derived
neurotrophic factor (GDNF) in the retinal degeneration
(rd/rd) mouse model of human retinitis pigmentosa.
Subretinal injections of GDNF were made into rd/rd mice
at 13 and 17 days of age and electroretinograms (ERGs) recorded at 22
days. Control mice received saline vehicle injections or underwent no
procedure. At 23 days of age, retinas from treated and control mice
were fixed and processed for wholemount immunohistochemistry using an
anti-rod opsin antibody, and rod numbers were estimated using an
unbiased stereological systematic random approach. Subsequent to
counting, immunolabeled retinas were re-embedded and sectioned in a
transverse plane and the numbers of rods recalculated.
Although ERGs could not be recorded from sham-operation or nonsurgical rd/rd mice at 22 days of age, detectable responses (both
a- and b-waves) were observed in 4 of 10 GDNF-treated mice.
Stereological assessment of immunolabeled rods at 23 days showed that
control rd/rd retinas contained 41,880 ± 3,890
(mean ± SEM; n = 6), phosphate-buffered saline
(PBS)–injected retinas contained 61,165 ± 4,932 (n= 10; P < 0.001 versus control retinas)
and GDNF-injected retinas contained 89,232 ± 8,033 (n= 10; P < 0.001 versus control retinas, P < 0.002 versus PBS). This increase in rod
numbers after GDNF treatment was confirmed by cell counts obtained from
GDNF exerts both histologic and functional neuroprotective effects on
rod photoreceptors in the rd/rd mouse. Thus rescue was
demonstrated in an animal model of inherited retinal degeneration in
which the gene defect was located within the rods themselves, similar
to most forms of human retinitis pigmentosa. GDNF represents a
candidate neurotrophic factor for palliating some forms of hereditary
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