Abstract
Purpose :
To determine the efficacy of retinal blockade achieved by intraocular injection of tetrodotoxin (TTX) in non-human primates (NHP), a potential “pharmacological occlusion therapy (eye patching)”. Intraocular injection of TTX has been studied extensively in kitten models of deprivation amblyopia. TTX injections have also been used in sedated NHP to abolish or reduce retinal ganglion cell responses. Here we describe TTX effects on visual functions in awake, behaving NHP.
Methods :
Recordings were obtained in 2 male macaque monkeys, mean age 6.8 yrs. TTX was injected through the pars plana of one eye at a concentration 3.8-8 μM and volume 30-60 μl. Three injections were performed per animal, each spaced 2-3 weeks apart. The animals’ visual acuity (VA) in each eye was measured using SSVEP (stimulus 0.6 Hz, 20 cpd); pupillary light responses were measured as relative afferent pupillary defects (RAPD); and optokinetic eye movements (OKN) were recorded before (baseline) and for several days after (day 1 – 3, D1 – D3) uniocular TTX injections.
Results :
Retinal blockade in the treated eye was evident after each injection for durations of at least 72 hours. SSVEP visual acuity at baseline was an average 19.5 – 23.3 cpd. VA on D1 was non-recordable; D2 was 8.9 – 11.8 cpd; and D3 9.1 – 11.2 cpd. RAPD showed reduction of the pupillary light response of 85-90% on D1; 45-61% on D2; and 24-43% on D3. OKN evoked slow-phase responses reduced 88 – 79% on D1; 67 – 55% on D2; and 24 –33% on D3. At approximately one week after injection all measures had returned to baseline range in the injected eye, i.e. there was no evidence of persistent blockade. Responses of the fellow, non-injected eye were normal at each testing interval.
Conclusions :
TTX appears to be an effective means for achieving substantial reduction in visual functions in the injected eye of awake, behaving NHPs. Visual acuity, RAPD and OKN were devastated by TTX for durations of up to 72 hours after each injection with no evidence of persistent retinal toxicity. TTX may be an effective method of “pharmacologic occlusion therapy” for future studies of amblyopia treatment in NHPs.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.