Longitudinal evaluation of immediate inflammatory responses after intravitreal AAV2 injection in rats by optical coherence tomography

Longitudinal Evaluation of Hyper-Reflective Foci in the Retina Following Subretinal Delivery of Adeno-Associated Virus in Non-Human Primates

“…This kinetic has been also observed in experiments using rats, in which, upon intravitreal injections of rAAV2, there was an increase in the number of HRF in the retina. 9 The observed deviations in our results may well reflect variability in the surgery. A difference in surgical trauma could contribute to a difference in numbers of HRF that potentially becomes enhanced in presence of high doses of rAAV8 at later time points.…”

“…This kinetic has been also observed in experiments using rats, in which, upon intravitreal injections of rAAV2, there was an increase in the number of HRF in the retina. 9 …”

“…[1][2][3][4][5][6] Depending on factors, such as dose, route of administration, rAAV capsid, and transgene expression, discrete hyper-reflective elements or hyper-reflective foci (HRF), might appear in spectral-domain optical coherence tomography (SD-OCT) scans as a potential indicator of a cellular immune response in the retina. 5 Even though the appearance of HRF after gene therapy remains ill defined, the presence of HRF in the outer retinal layers 7 could be a potential indicator of immune responses in the form of cellular activation/infiltration by immune-competent cells 6,8,9 associated to the surgical procedure, the rAAV treatment, or a combination of both. Coscas et al suggested that HRF could represent microglia cell activation when they first described the existence of HRF in age-related macular degeneration (AMD).…”

Systemic and local immune responses to intraocular AAV vector administration in non-human primates

“… 9 , 33 Hence, intravitreal AAV injections are expected to be more immunogenic than subretinal injections. 18 , 34 , 35 A study showed that an intravitreal (IVT) injection in one eye results in an immune response in the contralateral eye. This prevented a second IVT injection in the fellow eye, but a subretinal (SR) injection was possible.…”

Systemic and local immune response to intraocular AAV vector administration in non-human primates

“…In the vitreal space there are higher chances of exposure to systemic circulation 15 , whereas the subretinal space does not expose AAV to systemic circulation owing to the blood-retina barrier 33,9 . Hence intravitreal AAV injections are expected to be more immunogenic than subretinal injections 34,35,18 . A study showed that IVT in one eye results in an immune response in the contralateral eye.…”