In vivo assessments of retinal structure and function, and anterograde optic nerve transport after whole eye transplantation

Abstract

Purpose : We aim to assess retinal structural integrity, anterograde transport of the visual system and retinal function with optical coherence tomography (OCT), manganese (Mn)-enhanced MRI (MEMRI) and electroretinography (ERG) in our recently established whole eye transplantation (WET) rat model.

Methods : Syngeneic orthotopic WET were performed to the right eyes of 9 Lewis rats (Fig.1-A) The donor flaps consisted of tissue anterior to the optic chiasm, a section of temporal bone and skin of the eyelid and external ear. A similar region of tissue was removed in the recipient with the exception of the optic nerve (ON), which was cut at the base of the globe. ON coaptations, anastomoses of carotid arteries and external jugular veins were performed between donors and recipients. OCT was performed at week 1 after WET (n=7). MEMRI was performed at week 3 to evaluate anterograde Mn transport along the visual pathway after binocular intravitreal Mn injections. ERG was performed at week 7 in 2 separate animals to evaluate retinal function.

Results : OCT revealed visualization of retinal layers in 5 of the 7 transplanted eyes examined (Fig.1-B), whereas the other 2 eyes had corneal opacities that prevented visualization. MEMRI showed that after intravitreal Mn injections to both eyes, Mn transported anterogradely from the left, untreated eye to the right visual brain centers (Fig.2). Mn enhancement was also observed in the right, transplanted donor eye and intraorbital ON when compared to the eye and visual system prior to Mn injections. No apparent difference in Mn enhancement was observed between left naïve and right transplanted intraorbital ON. No apparent Mn enhancement was observed in the right recipient prechiasmatic ON, left lateral geniculate nucleus or left superior colliculus. In ERG, the transplanted eyes showed a-and b-waves in response to light stimulation.

Conclusions : OCT imaging revealed the existence of retinal layers after WET. MEMRI data suggested the presence of anterograde Mn transport from the donor eye to the optic nerve up to the site of transection. ERG data suggested some responses to light stimuli in the photoreceptors of transplanted eyes. The ocular viability seen after WET allows the potential for future therapeutic strategies for neuroprotection, ON regeneration and vision restoration.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.