Purchase this article with an account.
Tsung-Han Chou, Rajeshwari D Koilkonda, William J Feuer, Hong Yu, Vittorio Porciatti; Potency study of high-titer AAV2 gene therapy for treating Leber Hereditary Optic Neuropathy (LHON) in a preclinical mouse model.. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1187.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To test the efficacy of high-dose of AAV2(Y444,500,730F)-P1ND4v2 vector obtained from Children's Hospital of Philadelphia (CHOP) to rescue retinal ganglion cell (RGC) structure and function in a mouse model of LHON.
Thirty DBA/1J mice were separated into three groups: Naive Controls (NC, n=10); Mock LHON controls (MC, n=10) intravitreally injected in both eyes with ScAAV2-HSP-ND4(G11778A) (4.32E+12 vg/ml, 1μl) followed by a second injection ScAAV2-mCherry (4.32E+12 vg/ml, 1 μl); Gene Therapy (GT, n=10) intravitreally injected in both eyes with ScAAV2-HSP-ND4(G11778A) (4.32E+12 vg/ml, 1μl) followed by a second injection with CHOP test article (TA) ScAAV2-(Y444,500,730F)-P1ND4v2 (High Dose, 4.5E+12 vg/ml, 1.5 μl). Pattern electroretinograms (PERG) were recorded between 3- and 12-months post injections. At one-year post-injection, cell density in RGC layer (H&E staining) and axon density in the optic nerve (TEM) were determined (n=3 in each group).
While in the MC group the mean PERG amplitude decreased by about 20 % over time (GEE, p=0.01) it did not change in the GT and NC groups (GEE, p<0.05: NC>MC; GT>MC). At endpoint, the mean RGC layer cell density and optic nerve axon densities were on average reduced in the MC group by about 9% and 10%, respectively, compared to NC and GT groups.
High titer CHOP TA appeared to have a protective role on RGC function and structure in mice with optic neuropathy induced by mutant ND4.
This is a 2021 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only