Abstract
Purpose:
Active subretinal implants are highly complex, constantly improved devices requiring sophisticated surgical procedures. Under certain circumstances corrections, such as realignments, explantations, and reimplantations become necessary. Intraocular tissue reactions to devices, e.g. from scleral, retinal or RPE cells, have been described on a histologic (Gekeler, ARVO 2010) but not on a proteomic level.
Methods:
34 patients have been implanted with a subretinal MPDA; 2 patients underwent re-alignment (avg. 1.5), 10 patients after the pilot trial had explantation (avg. 9.5), and 1 re-implantation surgery (2.5, all in months). 3 removed implants were analyzed using liquid chromatography coupled to electrospray Orbitrap mass spectrometry (nHPLC-MS/MS) following limited proteolysis of the proteins that covered the surfaces.
Results:
Longer intervals since implantation resulted in more scarring around the polyimide (PI) foil on the sclera but no adhesion was found; implants were retrieved in 2-3 pieces, unharmed for technical analyses. PI foils and MPDAs were pulled out without silicone oil exchange. One patient (with initial subretinal hemorrhage) suffered from retinal detachment after explantation requiring oil exchange. Retinas over the MPDA remained unaltered in funduscopy and SD-OCT. In case of the first explant, proteomic analysis exhibited more than 900 protein identifications over the MPDA and 364 on the section of the implant on the sclera. Besides a huge overlap of common housekeeping, e.g. GAP-dehydrogenase and aldolase, and plasma proteins like serotransferrin a set of eye-, and/or retina-specific proteins like alpha-crystallin, beta arrestin and retinol-converting enzymes were identified from the chip section. All sections of the explanted device showed slight coverage by immunoreactive proteins like immunglobulins lambda and J, integrins alpha and beta, and by complement factors.
Conclusions:
Explantation and reimplantation surgery is feasible in subretinal implants as tissue reactions in the subretinal space are minimal. Proteomic analyses of explanted subretinal MPDAs revealed common protein sets on the surface as reported for other types of implants, e.g. silicone devices, reflecting both, minor irritation of the surrounding tissue and the body’s tendency to coat implants with an extracellular matrix. Proteomics can be valuable to improve biocompatibility tests in retinal implants.
Keywords: 663 proteomics •
702 retinitis