Effects of femtosecond laser-assisted minimally invasive lamellar keratoplasty (FL-MILK) on mild-to-moderate and advanced keratoconus.

PURPOSE: To compare the outcomes of femtosecond laser-assisted minimally invasive lamellar keratoplasty (FL-MILK) for mild-to-moderate keratoconus (KC) and advanced KC. METHODS: Prospective case series study. Sixty-three eyes of 56 patients with progressive KC underwent FL-MILK were divided into group 1 [mean keratometry (Kmean) ≤ 53D] and group 2 (Kmean > 53D). Best spectacle-corrected visual acuity (BSCVA), Kmean, maximum keratometry (Kmax), anterior central corneal elevation (ACE), stiffness parameter A1 (SP-A1) and deformation amplitude (DA) were evaluated preoperatively and up to 24 months postoperatively. RESULTS: Mean BSCVA improved from 0.34 ± 0.13 logMAR preoperatively to 0.25 ± 0.13 logMAR at 24 months postoperatively in group 1 (F = 10.10, P < .0001), and from 0.54 ± 0.31 logMAR to 0.40 ± 0.26 logMAR (F = 9.06, P = .0002) in group 2. Group 2 showed an average Kmax reduction of 10.9 D and an average Kmean reduction of 3.9 D at 24 months postoperatively (both P < .0001), whereas no significant change was observed in group 1. Average ACE decreased from 19.2 ± 10.0 to 5.2 ± 8.4 at 24 months postoperatively in group 1 (F = 28.5, P < .0001), and from 46.2 ± 16.3 to 19.1 ± 9.0 (F = 49.6, P < .0001) in group 2; SP-A1 increased from 53.8 ± 12.7 mmHg/mm to 95.9 ± 20.2 mmHg/mm in group 1 (F = 70.0, P < .0001), and from 38.6 ± 13.4 mmHg/mm to 89.3 ± 18.2 mmHg/mm (F = 96.9, P < .0001) in group 2; DA decreased from 1.30 ± 0.14 mm to 1.17 ± 0.13 mm in group 1 (F = 14.0, P < .0001), and from 1.40 ± 0.16 mm to 1.18 ± 0.10 mm (F = 27.6, P < .0001) in group 2. CONCLUSIONS: FL-MILK can stabilize progressive KC in mild-to-moderate cases and advanced cases at 24-month follow-up. Steeper corneas are more likely to undergo flattening after FL-MILK. CLINICAL TRIAL: Date of registration: July 16, 2017. The title of the trail: www. CLINICALTRIALS: gov Trial registration number: NCT03229239. The name of the trial registry: ClinicalTrials.gov.

Changes in aberrations and biomechanics after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in eyes with high astigmatism: a retrospective case control study.

BACKGROUND: To compare the 6-month changes in aberration and biomechanics after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for high astigmatism. METHODS: In this retrospective case control study, 47 eyes with high astigmatism (≥ 2.5 D, HA group) and 47 eyes with low astigmatism (≤ 1.0 D, LA group) underwent FS-LASIK. Preoperative and follow-up examinations included visual outcomes, higher order aberrations (HOAs) and biomechanics. Biomechanical parameters include a deformation amplitude ratio of 2 mm (DA ratio 2 mm), integrated inverse radius (IIR), stiffness parameter at first applanation (SP-A1), and ambrosio relational thickness through the horizontal meridian (ARTh). RESULTS: Six months postoperatively, there was no significant difference in the efficacy and safety index (both P > 0.05) between the two groups, but the cylinder was higher in the HA group. The HOAs increased significantly after surgery in both groups (all P < 0.05). Six months postoperatively, the changes in spherical aberration and HOAs were larger in the HA group (both P < 0.005), but there was no significant difference between the changes in coma (P > 0.05). Significant decreases in SP-A1 and ARTh and significant increases in the IIR and DA ratio of 2 mm (all P < 0.05) were observed after surgery in both groups. The changes in the DA ratio 2 mm, IIR, SP-A1, and ARTh were not significantly different between the groups. CONCLUSION: FS-LASIK had relative comparable efficacy and safety in correcting high and low myopic astigmatism, with higher astigmatic under-correction in eyes with high astigmatism. High astigmatism in eyes after FS-LASIK could introduce larger corneal aberrations, but the impact on corneal stiffness was the same as that in eyes with low astigmatism.

Comparison of central corneal thickness treated with small incision lenticule extraction, femtosecond laser-assisted in situ keratomileusis, or laser-assisted subepithelial keratomileusis for myopia.

To compare the central corneal thickness (CCT) treated with small incision lenticule extraction (SMILE), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), or laser-assisted subepithelial keratomileusis (LASEK) for myopia correction. This was a retrospective case series study. Patients who had completed 1-year follow-up after receiving SMILE, FS-LASIK, or LASEK at our hospital from January 2019 to July 2021 were included. Pentacam pachymetry was performed to measure the CCT. The predicted CCT reduction was obtained through laser platform. The measured CCT reduction was defined as the difference between the preoperative and postoperative CCT using Pentacam pachymetry. There were 100 eyes treated by SMILE, 100 eyes by FS-LASIK, and 100 eyes by LASEK. There was a significant difference in predicted CCT reduction among the three surgeries (P < 0.001), but no significant difference in measured CCT reduction postoperatively (PGroup = 0.373). At 1 year postoperatively, the CCT reduction was overestimated by 17.85 ± 5.36 µm in the SMILE group, underestimated by 4.31 ± 7.08 µm in the FS-LASIK group, and underestimated by 7.60 ± 8.28 µm in the LASEK group (PGroup < 0.001, PTime < 0.001). In the FS-LASIK group, the difference between predicted and measured CCT reduction was not related to the predicted CCT reduction (P = 0.095). The laser platform may overestimate the CCT reduction for SMILE and underestimate it for FS-LASIK and LASEK. FS-LASIK has a much higher level of accuracy in CCT reduction, which is not influenced by refractive correction.

Global and Regional Damages in Retinal Ganglion Cell Axon Bundles Monitored Non-Invasively by Visible-Light Optical Coherence Tomography Fibergraphy.

Retinal ganglion cells (RGCs) exhibit compartmentalized organization, receiving synaptic inputs through their dendrites and transmitting visual information from the retina to the brain through the optic nerve. Little is known about the structure of RGC axon bundles extending from individual RGC somas to the optic nerve head (ONH) and how they respond to disease insults. We recently introduced visible-light optical coherence tomography fibergraphy (vis-OCTF), a technique for directly visualizing and analyzing mouse RGC axon bundles in vivo In this study, we validated vis-OCTF's ability to quantify RGC axon bundles with an increased number of RGCs using mice deficient in BCL2-associated X protein (BAX-/-). Next, we performed optic nerve crush (ONC) injury on wild-type (WT) mice and showed that the changes in RGC axon bundle width and thickness were location-dependent. Our work demonstrates the potential of vis-OCTF to longitudinally quantify and track RGC damage at single axon bundle level in optic neuropathies.SIGNIFICANCE STATEMENT Nearly all clinical and preclinical studies measure the retinal nerve fiber (RNFL) thickness as the sole indicator of retinal ganglion cell (RGC) damage without investigating RGC axon bundles directly. We demonstrated visible-light optical coherence tomography fibergraphy (vis-OCTF) to directly quantify global and regional RGC axon bundle organizations in vivo as a new biomarker for RGC health. We validated in vivo vis-OCTF measures using both confocal microscopy of the immunostained flat-mounted retina and numerical simulations. Vis-OCTF for monitoring RGC axon bundle organization has the potential to bring new insight into RGC damage in optic neuropathies.

Long-term retinal protection by MEK inhibition in Pax6 haploinsufficiency mice.

Aniridia is a panocular condition characterized by impaired eye development and vision, which is mainly due to the haploinsufficiency of the paired-box-6 (PAX6) gene. Like what is seen in aniridia patients, Pax6-deficient mice Pax6Sey-Neu/+ exhibit a varied degree of ocular damage and impaired vision. Our previous studies showed that these phenotypes were partially rescued by PD0325901, a mitogen-activated protein kinase kinase (MEK or MAP2K) inhibitor. In this study, we assessed the long-term efficacy of PD0325901 treatment in retinal health and visual behavior. At about one year after the postnatal treatment with PD0325901, Pax6Sey-Neu/+ mice showed robust improvements in retina size and visual acuity, and the elevated intraocular pressure (IOP) was also alleviated, compared to age-matched mice treated with vehicles only. Moreover, the Pax6Sey-Neu/+ eyes showed disorganized retinal ganglion cell (RGC) axon bundles and retinal layers, which we termed as hotspots. We found that the PD treatment reduced the number and size of hotspots in the Pax6Sey-Neu/+ retinas. Taken together, our results suggest that PD0325901 may serve as an efficacious intervention in protecting retina and visual function in aniridia-afflicted subjects.

Femtosecond laser-assisted minimally invasive lamellar keratoplasty for the treatment of advanced keratoconus.

BACKGROUND: To evaluate the initial safety and efficacy of femtosecond laser-assisted minimal invasive lamellar keratoplasty (FL-MILK) for advanced keratoconus. METHODS: Twenty-two patients (22 eyes) with advanced keratoconus were included in this prospective study. All the involved eyes underwent FL-MILK. The femtosecond laser was used to create an intrastromal pocket with a 2.3 mm incision in the recipient cornea. Then a stromal button with a diameter of 9.0 mm and a depth of 200 µm was gently inserted into the intrastromal pocket through the 2.3 mm incision and flattened. No sutures were applied. Follow-up was conducted for 24 months. RESULTS: Twenty-two patients completed follow-up data for 12 months, 16 patients had 24 months follow-up. No epithelial implantation, infection or allogeneic rejection were observed during the follow-up. Based on baseline values, postoperative 12 months values and postoperative 24 months values, clinical significantly improvement was recorded in corrected distance visual acuity (CDVA) (0.40 ± 0.18 logMAR vs. 0.30 ± 0.12 logMAR and 0.23 ± 0.13 logMAR), the anterior central corneal elevation (29.14 ± 15.33 µm vs. 14.45 ± 13.75µm and 11.38 ± 8.33 µm), and corneal higher-order aberrations (3.536 ± 1.503 vs. 2.761 ± 1.517 and 0.994 ± 0.391). Corneal biomechanical properties in all eyes improved significantly. SP-A1 increased from 48.64 ± 12.87 preoperatively to 87.26 ± 21.01 postoperative 12 months and 88.77 ± 18.26 postoperative 24 months; deformation amplitude (DA) decreased from 1.36 ± 0.15 preoperatively to 1.21 ± 0.12 postoperative 12 months and 1.19 ± 0.19 postoperative 24 months. CONCLUSIONS: Initial experience suggests that this minimally invasive transplantation may be a feasible option for advanced keratoconus. A larger cohort and longer follow-up are required to validate our results and establish long-term safety and efficacy of the procedure.

In vivo imaging of the inner retinal layer structure in mice after eye-opening using visible-light optical coherence tomography.

The growth of the mouse eye and retina after birth is a dynamic, highly regulated process. In this study, we applied visible-light optical coherence tomography (vis-OCT), a non-invasive imaging technique, to examine developing retinal layer structures after eye-opening. We introduced a resampled circumpapillary B-scan averaging technique to improve the inter-layer contrast, enabling retinal layer thickness measurements as early as postnatal day 13 (P13) - right after eye-opening. We confirmed vis-OCT measurements using ex vivo confocal microscopy of retinal sections at different ages. Our results demonstrate that vis-OCT can visualize the developmental murine retinal layer structure in vivo, which offers us new opportunities to better characterize the pathological alterations in mouse models of developmental eye diseases.

Primary Eccrine Porocarcinoma of the Thumb With Metastasis: A Rare Case Report and Literature Review.

ABSTRACT: Eccrine porocarcinoma (EPC) is a rare malignant sweat gland tumor that accounts for approximately 0.005% of all cutaneous carcinomas. It favors the lower extremities. Only 3% of EPCs are on the hand, and only 6 cases occurring specifically on fingers have been previously documented. However, we met a patient with EPC presenting the primary lesion on the left thumb and an extensive cutaneous metastasis on the left forearm. Pathologic findings of axillary lymph nodes confirmed lymphatic metastasis.

Clinical outcomes of double continuous suture in femtosecond laser-assisted lamellar keratoplasty for keratoconus.

To assess the surgical outcomes in patients who underwent femtosecond laser-assisted lamellar keratoplasty with double continuous suture for keratoconus, 100 patients (102 eyes) with keratoconus in advanced stages undergoing femtosecond laser-assisted lamellar keratoplasty in Shandong Eye Hospital were studied. In the management of keratoconus, 50 patients (52 eyes) received double continuous suture, and 50 patients (50 eyes) underwent interrupted suture. The follow-up duration was 1 year. Best-corrected visual acuity (BCVA), corneal astigmatism, cosmetic outcomes, and surgical complications were measured as outcome indicators. The epithelium healed at 3 ± 2 days and 4 ± 2 days in the double continuous suture group and the interrupted suture groups, respectively (P > 0.05). At 6 months after surgery, the average visual acuity was 20/125 and 20/100 (P > 0.05), and the average BCVA was 20/32 and 20/40 (P > 0.05), respectively. At 1 year after surgery, the average visual acuity was 20/63 and 20/80 (P > 0.05), and the average BCVA was 20/32 and 20/25 (P > 0.05), respectively; the mean curvature was 43.24 ± 5.15 D and 43.31 ± 5.58 D (P > 0.05), the mean astigmatism was 3.21 ± 1.74 D and 5.35 ± 1.37 D (P < 0.05).The looseness of sutures were found in 2 patients and 15 patients in both groups, respectively (P < 0.05). No postoperative infection or immune rejection occurred in either group during the follow-up. Comparing with the interrupted suture, using the continuous suture in femtosecond laser-assisted lamellar keratoplasty for keratoconus markedly limited the looseness of sutures with lesser corneal astigmatism and better visual quality postoperative.

Postoperative corneal biomechanics and influencing factors during femtosecond-assisted laser in situ keratomileusis (FS-LASIK) and laser-assisted subepithelial keratomileusis (LASEK) for high myopia.

The purpose of this study is to compare the postoperative corneal biomechanics and assess the influence factors after femtosecond-assisted laser in situ keratomileusis (FS-LASIK) and laser-assisted subepithelial keratomileusis (LASEK) for high myopia. In this retrospective study, patients who completed 1-year follow-up were included. The corneal biomechanical parameters, including deformation amplitude ratio 2.0 mm (DA ratio 2.0 mm), integrated inverse radius (IntInv Rad), stiffness parameter at first applanation (SP-A1), and Ambrosio relational thickness through the horizontal meridian (ARTh), were measured with Corvis STII. We also investigated the relationship between these biomechanics and preoperative or intraoperative variables. Thirty eyes had FS-LASIK and 30 eyes had LASEK. The changes in DA ratio 2.0 mm, IntInv Rad, and SP-A1 after surgery were significantly smaller in the LASEK group than in the FS-LASIK group, while the change in the ARTh was not significantly different between groups. No significant differences were detected in the mean values of postoperative DA ratio 2.0 mm, IntInv Rad, and SP-A1 between LASEK and FS-LASIK, while significant difference was detected in the mean value of postoperative ARTh. There was a significant correlation between the resident stromal bed thickness and the postoperative DA ratio 2.0 mm, IntInv Rad, or SP-A1. The postoperative ARTh has shown significant correlation with postoperative central corneal thickness and the amount of myopic correction. The effect of LASEK on corneal biomechanics was smaller than FS-LASIK when the same central corneal thickness was consumed. LASEK may be performed with a lower risk of postoperative corneal ectasia than FS-LASIK.

Individualized endoscopic management strategy for impacting jujube pits in the upper gastrointestinal tract: a 3-year single-center experience in northern China.

BACKGROUND: Impaction of jujube pits in the upper gastrointestinal (GI) tract is a special clinical condition in the northern Chinese population. Endoscopic removal is the preferred therapy, but there is no consensus on the management strategies. We reported our individualized endoscopic strategies on the jujube pits impacted in the upper GI tract. METHODS: In this retrospective study, we included 191 patients (male: 57; female: 134) who presented to our hospital with ingestion of jujube pits between January 2015 and December 2017. Demographic information, times of hospital visiting, locations of jujube pits, endoscopic procedures, post-extraction endoscopic characteristics were analyzed. Management strategies including sufficient suction, repeated irrigation, jejunal nutrition and gastrointestinal decompression were given based on post-extraction endoscopic characteristics and impacted locations. RESULTS: Peak incidence was in the second quarter of each year (85/191 cases, 44.5%). Among the 191 cases, 169 (88.5%) showed pits impaction in the esophagus, 20 (10.5%) in the prepyloric region and 2 (1.0%) in the duodenal bulb. A total of 185 patients (96.9%) had pits removed with alligator jaw forceps, and 6 (3.1%) underwent suction removal with transparent caps placed over the end of the endoscope to prevent injury on removal of these pits with two sharp painted edges. Post-extraction endoscopic manifestations included mucosal erosion (26.7%), mucosa laceration (24.6%), ulceration with a white coating (18.9%) and penetrating trauma with pus cavity formation (29.8%). All patients received individualized endoscopic and subsequent management strategies and showed good outcomes. CONCLUSIONS: Individualized endoscopic management for impacted jujube pits in the upper GI tract based on post-extraction endoscopic characteristics and impacted locations was safe, effective, and minimally invasive.

SAP102 regulates synaptic AMPAR function through a CNIH-2-dependent mechanism.

The postsynaptic density (PSD)-95-like, disk-large (DLG) membrane-associated guanylate kinase (PSD/DLG-MAGUK) family of proteins scaffold α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complexes to the postsynaptic compartment and are postulated to orchestrate activity-dependent modulation of synaptic AMPAR functions. SAP102 is a key member of this family, present from early development, before PSD-95 and PSD-93, and throughout life. Here we investigate the role of SAP102 in synaptic transmission using a cell-restricted molecular replacement strategy, where SAP102 is expressed against the background of acute knockdown of endogenous PSD-95. We show that SAP102 rescues the decrease of AMPAR-mediated evoked excitatory postsynaptic currents (AMPAR eEPSCs) and AMPAR miniature EPSC (AMPAR mEPSC) frequency caused by acute knockdown of PSD-95. Further analysis of the mini events revealed that PSD-95-to-SAP102 replacement but not direct manipulation of PSD-95 increases the AMPAR mEPSC decay time. SAP102-mediated rescue of AMPAR eEPSCs requires AMPAR auxiliary subunit cornichon-2, whereas cornichon-2 knockdown did not affect PSD-95-mediated regulation of AMPAR eEPSC. Combining these observations, our data elucidate that PSD-95 and SAP102 differentially influence basic synaptic properties and synaptic current kinetics potentially via different AMPAR auxiliary subunits. NEW & NOTEWORTHY Synaptic scaffold proteins postsynaptic density (PSD)-95-like, disk-large (DLG) membrane-associated guanylate kinase (PSD-MAGUKs) regulate synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function. However, the functional diversity among different PSD-MAGUKs remains to be categorized. We show that distinct from PSD-95, SAP102 increase the AMPAR synaptic current decay time, and the effect of SAP102 on synaptic AMPAR function requires the AMPAR auxiliary subunit cornichon-2. Our data suggest that PSD-MAGUKs target and modulate different AMPAR complexes to exert specific experience-dependent modification of the excitatory circuit.

Visual Experience Is Required for the Development of Eye Movement Maps in the Mouse Superior Colliculus.

Topographic maps are a fundamental feature of the brain's representations of the sensory environment as well as an efficient way to organize motor control networks. Although great progress has been made in our understanding of sensory map development, very little is known about how topographic representations for motor control develop and interface with sensory maps. Here we map the representation for eye movements in the superior colliculus (SC) in awake mice. As stimulation sites were sampled along the anterior-posterior axis, small amplitude, nasally directed (ipsiversive) saccadic eye movements were evoked by microstimulation in anterior SC, followed by a smooth progression to large, temporally directed (contraversive) movements in posterior SC. This progressive change of movement amplitude and direction is consistent with the global polarity of the retinotopic map in the superficial SC, just as in primates and cats. We then investigated the role of visual experience in the development of eye movement map by studying mice reared in complete darkness. Saccades evoked by SC stimulation as well as spontaneous saccadic eye movements were larger in the dark-reared mice, indicating that visual experience is required to fine-tune the gain of saccades and to establish normal eye movement maps in the SC. Our experiments provide a foundation for future studies to investigate the synaptic organization and developmental mechanisms of sensorimotor transformations in mice. SIGNIFICANCE STATEMENT: The superior colliculus (SC) is a midbrain structure important for multisensory integration and sensorimotor transformation. Here we have studied eye movement representations in the SC of mice, a species that has become a popular model in vision research because of available genetic tools. Our studies show mice make saccadic eye movements spontaneously and in response to SC stimulation. The mouse SC contains an eye movement map that has the same global polarity as the overlaying visual map, just like in cats and primates. Furthermore, we show that visual experience is required for establishing the normal eye movement map. Our study provides a necessary basis for future mechanistic studies of how SC motor maps develop and become aligned with sensory maps.

TGF-ß1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG2 cells.

Liver cancer is one of the most common human malignancies, and transforming growth factor-beta (TGF-ß) pathway plays a key role in its pathogenesis. To study the relationship between TGF-ß pathway and the related protein expression of many signaling pathway, markers of stem cells, CK family, and others, liver cancer HepG2 cells were transfected with siRNA directed against TGF-ß1 or were treated with exogenous TGF-ß1. Then, these protein levels were measured by Western blotting. After siRNA transfection, TGF-ß1 protein level was decreased, indicating that the siRNA against it was effective. In exogenous TGF-ß1 group, the expression of smad4, smad2/3, and ß-catenin proteins was increased, whereas that of p-smad2/3, CD133, cleaved Notch1, and epithelial cell adhesion molecule (EpCAM) proteins at 48 h was decreased. The expression of CK8 and CK18 proteins was increased at 24 h and was decreased at 48 and 96 h. In TGF-ß1-silenced group, the expression of smad2/3, ß-catenin, cleaved-notch1, and CK18 proteins was decreased, while that of smad4, p-smad2/3, CD133, EpCAM, and CK8 proteins was increased. TERT protein expression was slightly increased in exogenous TGF-ß1 group at 48 h and in TGF-ß1-silenced group at 96 h. TGF-ß1 did not affect the protein expression of CK19 and HIF-1. Thus, TGF-ß1 pathway plays an important role in cell regulation of liver cancer through the modulation of these proteins. These data will contribute to the understanding of the pathogenesis of liver cancer and the role of TGF-ß pathway in this process.

Differential roles of postsynaptic density-93 isoforms in regulating synaptic transmission.

In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most variable paralog in this family; it exists in six different N-terminal isoforms. Probably because of the structural and functional variability of these isoforms, the synaptic role of PSD-93 remains controversial. To accurately characterize the synaptic role of PSD-93, we quantified the expression of all six isoforms in the mouse hippocampus and examined them individually in hippocampal synapses. Using molecular manipulations, including overexpression, gene knockdown, PSD-93 knock-out mice combined with biochemical assays, and slice electrophysiology both in rat and mice, we demonstrate that PSD-93 is required at different developmental synaptic states to maintain the strength of excitatory synaptic transmission. This strength is differentially regulated by the six isoforms of PSD-93, including regulations of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-active and inactive synapses, and activity-dependent modulations. Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission.

Differential requirement for NMDAR activity in SAP97ß-mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses.

PSD-95-like, disc-large (DLG) family membrane-associated guanylate kinase proteins (PSD/DLG-MAGUKs) are essential for regulating synaptic AMPA receptor (AMPAR) function and activity-dependent trafficking of AMPARs. Using a molecular replacement strategy to replace endogenous PSD-95 with SAP97ß, we show that the prototypic ß-isoform of the PSD-MAGUKs, SAP97ß, has distinct NMDA receptor (NMDAR)-dependent roles in regulating basic properties of AMPAR-containing synapses. SAP97ß enhances the number of AMPAR-containing synapses in an NMDAR-dependent manner, whereas its effect on the size of unitary synaptic response is not fully dependent on NMDAR activity. These effects contrast with those of PSD-95α, which increases both the number of AMPAR-containing synapses and the size of unitary synaptic responses, with or without NMDAR activity. Our results suggest that SAP97ß regulates synaptic AMPAR content by increasing surface expression of GluA1-containing AMPARs, whereas PSD-95α enhances synaptic AMPAR content presumably by increasing the synaptic scaffold capacity for synaptic AMPARs. Our approach delineates discrete effects of different PSD-MAGUKs on principal properties of glutamatergic synaptic transmission. Our results suggest that the molecular diversity of PSD-MAGUKs can provide rich molecular substrates for differential regulation of glutamatergic synapses in the brain.

Regional analysis of posterior corneal elevation after laser refractive surgeries for correction of myopia of different degrees.

PURPOSE: To evaluate regional changes in the posterior corneal elevation after three laser refractive surgeries for correction of myopia of different degrees. SETTINGS AND DESIGN: Retrospective, comparative, and non-randomized study. METHODS: Two hundred patients (200 eyes) who underwent laser epithelial keratoplasty (LASEK), femtosecond-assisted laser in-situ keratomileusis (FS-LASIK), and small-incision lenticule extraction (SMILE) were included in this study. According to preoperative spherical equivalent (SE), each surgical group was divided into two refractive subgroups: low-to-moderate myopia (LM group) and high myopia (H group). The posterior corneal elevation from Pentacam Scheimpflug tomography was analyzed preoperatively and at 1 month, 3 months, 6 months, and 12 months postoperatively. Three subregions of the posterior cornea were divided in this study as the central, paracentral, and peripheral regions. STATISTICAL ANALYSIS USED: Generalized Estimating Equations (GEE). RESULTS: For all three surgical groups, similar changing trends were seen in the two refractive subgroups. H group presented a larger changing magnitude than the LM group in FS-LASIK over time ( P < 0.05), whereas no significant difference was noted in the two refractive subgroups of LASEK or SMILE ( P > 0.05). At 12 months postoperatively, the central posterior corneal elevation returned to the preoperative level in LASEK ( P > 0.05) but shifted forward significantly in FS-LASIK and SMILE ( P < 0.05). CONCLUSION: Different posterior corneal regions respond differently to corneal refractive surgeries. LASEK, FS-LASIK, and SMILE demonstrate different trends in the regional changes in posterior corneal elevation. The corneal shape seems more stable in LASEK than in FS-LASIK and SMILE.

Comparative In Vivo Imaging of Retinal Structures in Tree Shrews, Humans, and Mice.

Rodent models, such as mice and rats, are commonly used to examine retinal ganglion cell damage in eye diseases. However, as nocturnal animals, rodent retinal structures differ from primates, imposing significant limitations in studying retinal pathology. Tree shrews (Tupaia belangeri) are small, diurnal paraprimates that exhibit superior visual acuity and color vision compared with mice. Like humans, tree shrews have a dense retinal nerve fiber layer (RNFL) and a thick ganglion cell layer (GCL), making them a valuable model for investigating optic neuropathies. In this study, we applied high-resolution visible-light optical coherence tomography to characterize the tree shrew retinal structure in vivo and compare it with that of humans and mice. We quantitatively characterize the tree shrew's retinal layer structure in vivo, specifically examining the sublayer structures within the inner plexiform layer (IPL) for the first time. Next, we conducted a comparative analysis of retinal layer structures among tree shrews, mice, and humans. We then validated our in vivo findings in the tree shrew inner retina using ex vivo confocal microscopy. The in vivo and ex vivo analyses of the shrew retina build the foundation for future work to accurately track and quantify the retinal structural changes in the IPL, GCL, and RNFL during the development and progression of human optic diseases.

Visible-Light Optical Coherence Tomography Fibergraphy of the Tree Shrew Retinal Ganglion Cell Axon Bundles.

We seek to develop techniques for high-resolution imaging of the tree shrew retina for visualizing and parameterizing retinal ganglion cell (RGC) axon bundles in vivo. We applied visible-light optical coherence tomography fibergraphy (vis-OCTF) and temporal speckle averaging (TSA) to visualize individual RGC axon bundles in the tree shrew retina. For the first time, we quantified individual RGC bundle width, height, and cross-sectional area and applied vis-OCT angiography (vis-OCTA) to visualize the retinal microvasculature in tree shrews. Throughout the retina, as the distance from the optic nerve head (ONH) increased from 0.5 mm to 2.5 mm, bundle width increased by 30%, height decreased by 67%, and cross-sectional area decreased by 36%. We also showed that axon bundles become vertically elongated as they converge toward the ONH. Ex vivo confocal microscopy of retinal flat-mounts immunostained with Tuj1 confirmed our in vivo vis-OCTF findings.