This work represents the first successful attempt to reconstruct the retinal lesion site in an adult mammal through tissue replacement using an embryonic retina grafting technique. We have also reported for the first time that an adult mammalian retina can be induced to initiate a wound repair response through trophic phenomena. These findings constitute a major breakthrough which should have dramatic implications and impact with respect to retina disease and trauma. More specifically, the further development and sophistication of these techniques as outlined in this proposal will hopefully allow for the eventual total reconstruction of damaged retinal tissue thus facilitating the process of visual system repair leading to functional recovery in man. The long term objectives of this work are to: (1) understand and help facilitate the process of retinal wound repair through the use of embryonic tissue implants and trophic factors; and (2) better understand the mechanisms of retinal development as it relates to trophic phenomena as well as through cell and tissue interractions.
The specific aims of this proposal are to: (1) begin a detailed characterization of the grafting phenomenon to determine the variables which will optimize the implantaiton process; (2) learn the nature of the graft/host cellular relationships and interconnections; (3) concentrate on sophistication of the grafting process to the point where the lost retinal tissue can be completely restored to its normal configuration; (4) identify the important temporal trophic events and mechanisms in the wound repair response initiated by peripheral nerve implants; (5) determine the cellular source(s) of the putative trophic factor(s) from the peripheral nerve that is responsible for the retinal wound repair response; and (6) compare and contrast the peripheral nerve neurotrophic retinal response to that of known neurotrophic factors like nerve growth factor and the new brain derived growth factor.
The specific aims of this proposal will be accomplished through the use of light microscopy, electron microscopy, microsurgery, tissue transplantation, immunocytochemistry, autoradiography, tissue culture, cryopreservation and opthalmoscopic techniques.
