Background ophthalmological changes following subretinal injection in the brown Norway rat

PurposeThe purpose of the study was to evaluate the background changes associated with transscleral subretinal injection in Brown Norway (BN) ratsMethodsFifteen BN rats received a bilateral transscleral subretinal injection of saline at a volume of 6 μL while under isoflurane anesthesia. The eyes were examined by slit lamp and indirect ophthalmoscope the day following injection and 1, 2, 3, 4, 8 and 12 weeks post injectionResultsProcedure-related changes included the following observations: Transient corneal opacities occurred in 16/30 eyes that were considered related to the anesthesia. Cataracts developed in 5/30 eyes associated with lens trauma at the time of dosing. Slight vitreous hemorrhages occurred post dose in 28/30 eyes, resolving in all but 2 eyes by 4 weeks. An area of focal depigmentation of the retina/choroid or white focal retinal opacity was seen at the needle insertion site at the retina in 22/30 eyes, resolving by 4 weeks for 13 eyes and persisting up to 12 weeks for the remaining 7. In the bleb itself, there were focal areas of irregular pigmentation in 13/30 eyes resolving in all but 2 eyes by week 4. The remaining 2 persisted up to week 12. This was considered secondary to the physical neuro-retinal separation caused by the bleb formation. Slight retinal/choroidal hemorrhages were also seen at the injection site in most eyes up to week 4ConclusionsIn conclusion, transscleral subretinal injection in BN rats generally resulted in slight ocular trauma that resolved in most eyes by 4 weeks post injection. It is important to take these changes into account when designing the study and evaluating therapeutics administered by this dose route.