Faculty Bibliography

UNLABELLED:There are over 43 million individuals in the world who are blind. As retinal ganglion cells are incapable of regeneration, treatment modalities for this condition are limited. Since first incepted in 1885, whole-eye transplantation (WET) has been proposed as the ultimate cure for blindness. As the field evolves, different aspects of the surgery have been individually explored, including allograft viability, retinal survival, and optic nerve regeneration. Due to the paucity in the WET literature, we aimed to systematically review proposed WET surgical techniques to assess surgical feasibility. Additionally, we hope to identify barriers to future clinical application and potential ethical concerns that could be raised with surgery. METHODS/UNASSIGNED:We conducted a systematic review of PubMed, Embase, Cochrane Library, and Scopus from inception to June 10, 2022, to identify articles pertaining to WET. Data collection included model organisms studied, surgical techniques utilized, and postoperative functional outcomes. RESULTS/UNASSIGNED:Our results yielded 33 articles, including 14 mammalian and 19 cold-blooded models. In studies performing microvascular anastomosis in mammals, 96% of allografts survived after surgery. With nervous coaptation, 82.9% of retinas had positive electroretinogram signals after surgery, indicating functional retinal cells after transplantation. Results on optic nerve function were inconclusive. Ocular-motor functionality was rarely addressed. CONCLUSIONS/UNASSIGNED:Regarding allograft survival, WET appears feasible with no complications to the recipient recorded in previous literature. Functional restoration is potentially achievable with a demonstrated positive retinal survival in live models. Nevertheless, the potential of optic nerve regeneration remains undetermined.

Osteoarthritis (OA) pathogenesis is associated with reduced chondrocyte homeostasis and increased levels of cartilage cellular senescence. Chondrosenescence is the development of cartilage senescence that increases with aging joints and disrupts chondrocyte homeostasis and is associated with OA. Adenosine A2A receptor (A2AR) activation in cartilage via intra-articular injection of liposomal A2AR agonist, liposomal-CGS21680, leads to cartilage regeneration in vivo and chondrocyte homeostasis. A2AR knockout mice develop early OA isolated chondrocytes demonstrate upregulated expression of cellular senescence and aging-associated genes. Based on these observations, we hypothesized that A2AR activation would ameliorate cartilage senescence. We found that A2AR stimulation of chondrocytes reduced beta-galactosidase staining and regulated levels and cell localization of common senescence mediators p21 and p16 in vitro in the human TC28a2 chondrocyte cell line. In vivo analysis similarly showed A2AR activation reduced nuclear p21 and p16 in obesity-induced OA mice injected with liposomal-CGS21680 and increased nuclear p21 and p16 in A2AR knockout mouse chondrocytes compared to wild-type mice. A2AR agonism also increased activity of the chondrocyte Sirt1/AMPK energy-sensing pathway by enhancing nuclear Sirt1 localization and upregulating T172-phosphorylated (active) AMPK protein levels. Lastly, A2AR activation in TC28a2 and primary human chondrocytes reduced wild-type p53 and concomitantly increased p53 alternative splicing leading to increase in an anti-senescent p53 variant, Δ133p53α. The results reported here indicate that A2AR signaling promotes chondrocyte homeostasis in vitro and reduces OA cartilage development in vivo by reducing chondrocyte senescence.

The modern approach to implant-based breast reconstruction encompasses an evolution in surgical techniques, patient selection, implant technology, and use of support materials. Successful outcomes are defined by teamwork throughout the ablative and reconstructive processes as well as appropriate and evidence-based utilization of modern material technologies. Patient education, focus on patient-reported outcomes, and informed and shared decision-making are the key to all steps of these procedures.