Growing evidence suggests that glial cells may have a role as neural precursors in the adult central nervous system. Although it has been shown that Mü ller cells exhibit progenitor characteristics in the postnatal chick and rat retinae, their progenitor-like role in developed human retina is unknown. We first reported the Mü ller glial characteristics of the spontaneously immortalized human cell line MIO-M1, but recently we have derived similar cell lines from the neural retina of several adult eye donors. Since immortalization is one of the main properties of stem cells, we investigated whether these cells expressed stem cell markers. Cells were grown as adherent monolayers, responded to epidermal growth factor, and could be expanded indefinitely without growth factors under normal culture conditions. They could be frozen and thawed without losing their characteristics. In the presence of extracellular matrix and fibroblast growth factor-2 or retinoic acid, they acquired neural morphology, formed neurospheres, and expressed neural stem cell markers including III tubulin, Sox2, Pax6, Chx10, and Notch 1. They also expressed markers of postmitotic retinal neurons, including peripherin, recoverin, calretinin, S-opsin, and Brn3. When grafted into the subretinal space of dystrophic Royal College of Surgeons rats or neonatal Lister hooded rats, immortalized cells migrated into the retina, where they expressed various markers of retinal neurons. These observations indicate that adult human neural retina harbors a population of cells that express both Mü ller glial and stem cell markers and suggest that these cells may have potential use for cell-based therapies to restore retinal function.
Aims To assess the efficacy of Xen in reducing intraocular pressure (IOP) in varying glaucoma subtypes. To assess the effect of combined phacoemulsification. To determine the frequency of complications and explore further bleb management needed. Methods Retrospective case note review of all patients undergoing Xen implantation across four centres from August 2015 to May 2017. Results In total, 259 consecutive surgeries of 226 patients were reviewed. IOP reduced from 19.3 (SD ± 6.0) mmHg preoperatively to 14.2 (SD ± 4.4) at month 12 and 13.5 (SD ± 3.3) at month 18 (p < 0.0001). Medication usage reduced from 2.6 (±1.1) preoperatively to 0.8 (±1.0) at month 12 (p < 0.0001) and 1.1 (±1.3) medications at month 18 (p < 0.0001). Simultaneous phacoemulsification did not alter outcomes as Xen IOP was 14.3 (SD ± 4.7) mmHg and Phaco-Xen was 13.8 (SD ± 2.6) mmHg at month 12 (p = 0.5367). Xen appears to be effective in previous failed filtration surgery. Adverse events included: IOP spikes of ≥30 mmHg in 33 (12.7%) cases, secondary filtration surgery required in 24 (9.3%) cases; implant exposure in 6 (2.3%) cases; persistent hypotonous maculopathy in 5 (1.9%) cases; persistent choroidal effusions in 4 (1.5%) cases; a cyclodialysis cleft secondary to implant insertion in 1 (0.5%) case; and 1 (0.5%) case of endophthalmitis postimplant bleb resuturing. In all, 40.9% of cases required postoperative bleb needling or antimetabolite injection. Conclusions Xen reduces IOP and medications at 18 months. Adverse events are uncommon. Careful postoperative surveillance and low threshold for bleb management is needed. Xen is safe and effective in mild to moderate glaucoma.
Müller glia with stem cell characteristics have been identified in the adult human eye, and although there is no evidence that they regenerate retina in vivo, they can be induced to grow and differentiate into retinal neurons in vitro. We differentiated human MEDICINE 2012;1:188 -199
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