Image registration of the human accommodating eye demonstrates equivalent increases in lens equatorial radius and central thickness

AIM: To compare the results of in vivo human high resolution image registration studies of the eye during accommodation to the predictions of mathematical and finite element models of accommodation. METHODS: Data from published high quality image registration studies of pilocarpine induced accommodative changes of equatorial lens radius(ELR) and central lens thickness(CLT) were statistically analyzed. RESULTS: The mean changes in ELR and CLT were 6.76 μm/diopter and 6.51 μm/diopter, respectively. The linear regressions, reflecting the association between ELR and accommodative amplitude(AAELR) was: slope=6.58 μm/diopter, r^2=0.98, P<0.0001 and between CLT and AACLT was: slope=6.75 μm/diopter, r^2=0.83, P<0.001. On the basis of these relationships, the CLT slope and the AAELR were used to predict the measured change in ELR(ELRpredicted). There was no statistical difference between ELRpredicted and the measured ELR as demonstrated by a Student's paired t-test: P=0.96 and linear regression analysis: slope=0.97, r^2=0.98, P<0.00001.CONCLUSION: Image registration with invariant positional references demonstrates that ELR and CLT equivalently minimally increase ~7.0 μm/diopter during accommodation. The small equivalent increases in ELRand CLT are associated with a large accommodative amplitude. These findings are consistent with the predictions of mathematical and finite element models that specified the stiffness of the lens nucleus is the same or greater than the lens cortex and that accommodation involves a small force(<5 g).

Cell replacement with stem cell-derived retinal ganglion cells from different protocols

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

Intracellular compartmentation of cAMP promotes neuroprotection and regeneration of CNS neurons

In the central nervous system（CNS）,cyclic adenosine monophosphate（cAMP）plays a critical role in numerous,often concurrent,neuronal functions including survival,growth,differentiation and synaptogenesis.

Compartmentalization of local cAMP signaling in neuronal growth and survival

Intracellular signal transduction controlling neuronal development and survival is conveyed by second messengers that are often differentially regulated over space and time.The highly polarized morphology of neurons is conferred by a network of regulatory signaling pathways that determine axon guidance and dendrite formation.Among these,cyclic adenosine monophosphate(cAMP)is a second messenger that is critical for numerous neuronal functions and known to activate and integrate a variety of downstream pathways.In the central nervous system(CNS),cAMP-dependent signaling is involved in growth cone motility,neuronal metabolism,axon extension in vitro,neuroprotection,and survival in vivo.The complexity of cAMP-dependent neuronal physiology and function raises fundamental questions about the mechanisms determining the specificity by which cAMP can regulate these processes.

A comparison of ophthalmic education in China and America

Training qualified ophthalmic professional is crucial for any eye care system worldwide.Education of modern western Ophthalmology in China started late but develops rapidly.This review focused on ophthalmic education in China and US,describing details of the programs and analyzing the differences.This summary may provide useful information for practitioners of medical education from both countries and help improve the present training designs.

Photoactivated growth factor release from bio-orthogonally crosslinkedhydrogels for the regeneration of corneal defects

In situ-forming hydrogels are an attractive option for corneal regeneration, and the delivery of growth factorsfrom such constructs have the potential to improve re-epithelialization and stromal remodeling. However,challenges persist in controlling the release of therapeutic molecules from hydrogels. Here, an in situ-forming bioorthogonallycrosslinked hydrogel containing growth factors tethered via photocleavable linkages (PC-HAColhydrogel) was developed to accelerate corneal regeneration. Epidermal growth factor (EGF) was conjugated tothe hydrogel backbone through photo-cleavable (PC) spacer arms and was released when exposed to mild intensityultraviolet (UV) light (2–5 mW/cm2, 365 nm). The PC-HACol hydrogel rapidly gelled within a few minuteswhen applied to corneal defects, with excellent transparency and biocompatibility. After subsequentexposure to UV irradiation, the hydrogel promoted the proliferation and migration of corneal epithelial cells invitro. The rate of re-epithelialization was positively correlated to the frequency of irradiation, verified through exvivo rabbit cornea organ culture studies. In an in vivo rat corneal wound healing study, the PC-HACol hydrogelexposed to UV light significantly promoted re-epithelialization, the remodeling of stromal layers, and exhibitedsignificant anti-scarring effects, with minimal α-SMA and robust ALDH3A1 expression. Normal differentiation ofthe regenerated epithelia after healing was evaluated by expression of the corneal epithelial biomarker, CK12.The remodeled cornea exhibited full recovery of corneal thickness and layer number without hyperplasia of theepithelium.

Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues

The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle glaucoma.However,the molecular basis and biological significance of the aging process in TM have not been fully elucidated.Here,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging.Furthermore,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two groups.Ultimately,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM function.Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range.Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

Identification and validation of key biomarkers and potential therapeutic targets for primary open-angle glaucoma

Primary open-angle glaucoma(POAG)is a prevalent cause of blindness worldwide,resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve.However,the underlying pathogenetic mechanisms of POAG are currently indistinct,and there has been no effective nonsurgical treatment regimen.The objective of this study is to identify novel biomarkers and potential therapeutic targets for POAG.The mRNA expression microarray datasets GSE27276 and GSE138125,as well as the single-cell high-throughput RNA sequencing(sc RNA-seq)dataset GSE148371 were utilized to screen POAGrelated differentially expressed genes(DEGs).Functional enrichment analyses,protein-protein interaction(PPI)analysis,and weighted gene co-expression network analysis(WGCNA)of the DEGs were performed.Subsequently,the hub genes were validated at a single-cell level,where trabecular cells were annotated,and the mRNA expression levels of target genes in different cell clusters were analyzed.Immunofluorescence and quantitative real-time PCR(q PCR)were performed for further validation.DEGs analysis identified 43 downregulated and 32 upregulated genes in POAG,which were mainly enriched in immune-related pathways,oxidative stress,and endoplasmic reticulum(ER)stress.PPI networks showed that FN1 and DUSP1 were the central hub nodes,while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by q PCR.Finally,FN1,GPX3,and VAV3 were determined to be pivotal core genes via single-cell validation.The relevant biomarkers involved in the pathogenesis of POAG,may serve as potential therapeutic targets.Further studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.