SummaryThe utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.
Athletes participating in contact sports such as ice hockey are exposed to a high risk of suffering a concussion. We determined whether recent rule changes regulating contact to the head introduced in 2010–11 and 2011–12 have been effective in reducing the incidence of concussion in the National Hockey League (NHL). A league with a longstanding ban on hits contacting the head, the Ontario Hockey League (OHL), was also studied. A retrospective study of NHL and OHL games for the 2009–10 to 2011–12 seasons was performed using official game records and team injury reports in addition to other media sources. Concussion incidence over the 3 seasons analyzed was 5.23 per 100 NHL regular season games and 5.05 per 100 OHL regular season games (IRR 1.04; 95% CI 1.01, 1.50). When injuries described as concussion-like or suspicious of concussion were included, incidences rose to 8.8 and 7.1 per 100 games respectively (IRR 1.23; 95% CI 0.81, 1.32). The number of NHL concussions or suspected concussions was lower in 2009–10 than in 2010–11 (IRR 0.61; 95% CI 0.45, 0.83), but did not increase from 2010–11 to 2011–12 (IRR 1.05; 95% CI 0.80, 1.38). 64.2% of NHL concussions were caused by bodychecking, and only 28.4% of concussions and 36.8% of suspected concussions were caused by illegal incidents. We conclude that rules regulating bodychecking to the head did not reduce the number of players suffering concussions during NHL regular season play and that further changes or stricter enforcement of existing rules may be required to minimize the risk of players suffering these injuries.
Current therapeutic antiangiogenic biologics used for the treatment of pathological ocular angiogenesis could have serious side effects due to their interference with normal blood vessel physiology. Here, we report the generation of novel antivascular endothelial growth factor-A (VEGF) biologics, termed VEGF “Sticky-traps,” with unique properties that allow for local inhibition of angiogenesis without detectable systemic side effects. Using genetic and pharmacological approaches, we demonstrated that Sticky-traps could locally inhibit angiogenesis to at least the same extent as the original VEGF-trap that also gains whole-body access. Sticky-traps did not cause systemic effects, as shown by uncompromised wound healing and normal tracheal vessel density. Moreover, if injected intravitreally, recombinant Sticky-trap remained localized to various regions of the eye, such as the inner-limiting membrane and ciliary body, for prolonged time periods, without gaining access either to the photoreceptors/choriocapillaris area or the circulation. These unique pharmacological characteristics of Sticky-trap could allow for safe treatment of pathological angiogenesis in patients with diabetic retinopathy and retinopathy of pre-maturity.
Optical coherence tomography (OCT) is a non-invasive, cost-efficient technique that provides high-resolution in vivo imaging of retinal tissue. The peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell complex (mGCC) are surrogate markers of neuroaxonal integrity in not only the eye, but also the central nervous system. Retinal atrophy may occur in tandem with central nervous system pathologies as a result of injury to ganglion cells, direct degeneration of the pregeniculate pathway, or retrograde transsynaptic degeneration secondary to postgeniculate lesions. In this review, we outline the basic principles of OCT and discuss its application to managing patients with demyelinating disorders, idiopathic intracranial hypertension, stroke, neurodegenerative conditions, and mitochondrial disorders. We demonstrate that measurements of pRNFL and mGCC thickness are paramount in diagnosing and monitoring neurologic disorders, including those with subclinical disease progression.
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