Studies of Structure and Function in Whole Eye Transplantation

Abstract

Purpose : The purpose of this study is to evaluate the structure and function of our orthotopic whole eye transplant model by assessing intraocular pressure (IOP), aqueous humor dynamics using gadolinium (Gd)-enhanced MRI, optic nerve structural integrity with diffusion tensor MRI (DTI) and functional return via electroretinography (ERG).

Methods : Syngeneic transplants were performed in 5 Lewis (RT1l) rats. IOP measurements were made using a TonoLab rebound tonometer. MRI: 0.3mmol/kg Gd-DTPA (Magnevist) was injected intraperitoneally after one T1- weighted image at baseline was acquired. Four animals were scanned at 3 weeks after transplantation, and 1 animal was scanned at 10 weeks after transplantation. Scans were performed using a 9.4-Tesla/31-cm Varian/Agilent scanner. ERG: Rats were placed in a black box overnight. An ERG system was integrated with a Dell PC equipped with a fast DSP microprocessor. Recording electrodes gently contacted the corneal surface of eyes precoated with a 2.5% hydroxypropyl-methylcellulose solution. A subdermal needle electrode served as common reference while another subdermal needle electrode was inserted at the base of the left leg. A Ganzfield delivered light stimuli with various stimulus strengths.

Results : IOPs of the naive and transplanted eye were 15.9±3.1 mmHg and 16.5±3.2 mmHg, respectively. At 3 weeks after transplantation, the right anterior chamber (AC) had a similar time to peak but a significantly lower peak intensity and lower initial increase rate than the left AC. At 10 weeks, the right AC had comparable peak intensity to the left AC. Limited Gd enhancement was observed in the vitreous with no significant difference between left and right eyes (two- tailed paired t-tests, p>0.05). T2-weighted images showed the donor optic nerve had comparable morphology with the uninjured intraorbital optic nerve at 3 weeks. DTI quantitation of the right injured optic nerve showed significantly lower FA and axial diffusivity by 54±6.1% and 24.9±5.7%, respectively, and a significant increase radial diffusivity by 83±29.5% compared to the left uninjured optic nerve (two-tailed paired t-tests, p<0.05). ERG revealed the lack of electrical responses to light stimuli in the transplanted eye.

Conclusions : A whole eye transplant model was established revealing the maintenance of aqueous humor dynamics, IOP and preserved integrity of the blood-ocular barriers of the transplanted eye.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.