Summary Adipose tissue–derived “stem cells” have been increasingly used by “stem-cell clinics” in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue–derived “stem cells” at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients’ severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients’ visual acuity ranged from 20/200 to no light perception.

BackgroundGlycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves glycosylphosphatidylinositol (GPI) anchors to regulate GPI-anchored protein activity at the cell surface. In the developing spinal cord, GDE2 utilizes its enzymatic function to regulate the production of specific classes of motor neurons and interneurons; however, GDE2’s roles beyond embryonic neurogenesis have yet to be defined.MethodUsing a panel of histological, immunohistochemical, electrophysiological, behavioral, and biochemistry techniques, we characterized the postnatal Gde2 −/− mouse for evidence of degenerative neuropathology. A conditional deletion of Gde2 was used to study the temporal requirements for GDE2 in neuronal survival. Biochemical approaches identified deficits in the processing of GPI-anchored GDE2 substrates in the SOD1 G93A mouse model of familial Amyotrophic Lateral Sclerosis that shows robust motor neuron degeneration.ResultsHere we show that GDE2 expression continues postnatally, and adult mice lacking GDE2 exhibit a slow, progressive neuronal degeneration with pathologies similar to human neurodegenerative disease. Early phenotypes include vacuolization, microgliosis, cytoskeletal accumulation, and lipofuscin deposition followed by astrogliosis and cell death. Remaining motor neurons exhibit peripheral motor unit restructuring causing behavioral motor deficits. Genetic ablation of GDE2 after embryonic neurogenesis is complete still elicits degenerative pathology, signifying that GDE2’s requirement for neuronal survival is distinct from its involvement in neuronal differentiation. Unbiased screens identify impaired processing of Glypican 4 and 6 in Gde2 null animals, and Glypican release is markedly reduced in SOD1 G93A mice.ConclusionsThis study identifies a novel function for GDE2 in neuronal survival and implicates deregulated GPI-anchored protein activity in pathways mediating neurodegeneration. These findings provide new molecular insight for neuropathologies found in multiple disease settings, and raise the possibility of GDE2 hypofunctionality as a component of neurodegenerative disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-017-0148-1) contains supplementary material, which is available to authorized users.

PurposeThe purpose of this study was to report clinical features and outcomes in patients with giant retinal tears (GRTs) undergoing vitreoretinal surgery and to compare data from this contemporary series to a previous study from the same institution.Materials and methodsA retrospective, interventional, consecutive case series was conducted for all patients diagnosed with GRTs who underwent vitreoretinal surgery between January 2011 and August 2017. Intraoperative data including the use of scleral buckling, perfluorocarbon liquid, and intraocular tamponade were collected and compared according to GRT size. These parameters, along with postoperative anatomic success and best-corrected visual acuity (BCVA), were compared with the previous series.ResultsThe study included 80 eyes of 79 patients with a presentation of retinal detachment with a GRT. Management approach for repair of GRT-associated retinal detachments included scleral buckle (SB) alone (three eyes, 4%), pars plana vitrectomy (PPV) (16 eyes, 20%), and combined SB/PPV (61 eyes, 76%). Perfluorocarbon liquids were used in 60/77 eyes (78%) undergoing PPV, and silicone oil was used in 54/77 eyes (70%). Single surgery success rate was in 69/80 eyes (86%). Eyes managed with SB (including SB alone and SB/PPV) or PPV without SB had similar rates of recurrent retinal detachment (16% vs 6%; P=0.33). Anatomic success was achieved in 76/80 eyes (95%) with one or more surgical procedures, and 54/80 eyes (68%) achieved postoperative BCVA of ≥20/400.ConclusionsIn the current series, repairs of retinal detachment due to GRTs were most commonly managed with combined PPV/SB and perfluorocarbon liquid, resulting in reasonably generally favorable anatomic and visual outcomes.

The mammalian cortex is a multilaminar structure consisting of specialized layer-specific neurons that form complex circuits throughout the brain and spinal cord. These neurons are generated in a defined sequence dictated by their birthdate such that early-born neurons settle in deep cortical layers whereas late-born neurons populate more superficial layers. Cortical neuronal birthdate is partly controlled by an intrinsic clock-type mechanism; however, the role of extrinsic factors in the temporal control of cell-cycle exit is less clear. Here, we show that Gde2, a six-transmembrane protein that induces spinal neuronal differentiation, is expressed in the developing cortex throughout cortical neurogenesis. In the absence of Gde2, cortical progenitors fail to exit the cell cycle on time, remain cycling, accumulate and exit the cell cycle en masse towards the end of the neurogenic period. These dynamic changes in cell-cycle progression cause deficits and delays in deep-layer neuronal differentiation and robust increases in superficial neuronal numbers. Gde2−/− cortices show elevated levels of Notch signaling coincident with when progenitors fail to differentiate, suggesting that abnormal Notch activation retains cells in a proliferative phase that biases them to superficial fates. However, no change in Notch signaling is observed at the time of increased cell-cycle exit. These observations define a key role for Gde2 in controlling cortical neuronal fates by regulating the timing of neurogenesis, and show that loss of Gde2 uncovers additional mechanisms that trigger remaining neuronal progenitors to differentiate at the end of the neurogenic period.