Changes in corneal innervation and pain responses in fungal keratitis

AIM: To characterize changes in the cornea nerve and pain responses in fungal keratitis(FK).METHODS: A retrospective analysis of in vivo confocal microscopy images of 11 FK corneas was performed, and the results were compared with those for 11 normal corneas. Subbasal corneal nerves were analyzed for total nerve number, main nerve trunk number, branching patterns and tortuosity. C57 BL/6 mice were infected with Aspergillus fumigatus. Disease severity was determined through clinical scoring and slit lamp photography. Corneas were harvested at 1, 3, 5, and 7 d post infection(p.i.) and assessed for β III tubulin. Corneal mechanical sensitivity thresholds were detected by von Frey test. β-endorphin(β-EP) and μ receptor protein expression was detected through Western blotting.RESULTS: Total nerve number, main nerve trunk number, and nerve branching were significantly lower in FK patients than in controls, but tortuosity was not significantly different. In infected mice, subbasal nerve density decreased from 1 d p.i., reaching a minimum at 5 d p.i. Clinical scores rose at 1 d p.i., peaked at 3 d p.i., and decreased at 5 d p.i. Mechanical sensitivity thresholds showed the same trends. β-EP and μ receptor protein expression increased after infection.CONCLUSION: Corneal nerve density is lower in FK patients and Aspergillus fumigatus-infected mice than in controls. Pain sensitivity decreases with postinfection corneal ulcer aggravation. β-EP and μ receptor proteins are both upregulated in infected mouse corneas.

Clinical associations of corneal neuromas with ocular surface diseases

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Knockout of TMEM206 in mice associated with a loss of corneal transparency

AIM:To investigate the role of transmembrane protein 206(TMEM206)in corneal edema in mice by knockout the TMEM206 gene using CRISPR/Cas9 editing technology.METHODS:TMEM206-knockout mice were generated using the CRISPR-Cas9 system.Variations in ophthalmic pathology were observed using slit lamp microscope and optical coherence tomography(OCT),intraocular pressure(IOP)was measured using a TonoLab Rebound Tonometer,and the ultrastructure of the corneal was observed using a transmission electron microscope.RESULTS:Corneal opacity was observed in 4/18 homozygous TMEM206^(-/-)mice whereas a similar change was not observed in heterozygous TMEM206^(+/-)mice and wild-type littermates.OCT examination showed that the mean central cornea thickness was 125±5.4μm in 4 homozygous TMEM206^(-/-)mice developed corneal edema and 115±1.2μm in wild-type mice(t=3.468,P<0.05)at 43wk.The mean IOP was 12.08±0.07 mm Hg in four right eyes with corneal edema and 12.03±0.03 mm Hg in three normal left eyes(P>0.05).Transmission electron microscopy revealed a disruption in the organization of the collagen fibrils in the central part of the cornea in homozygous TMEM206^(-/-)mice.CONCLUSION:TMEM206 is associated with corneal edema which caused organizational disruption of collagen fibrils in corneas of mice.

Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

Double intrastromal corneal ring segment implantation: a new approach for improved clinical outcomes in keratoconus patients

AIM:To evaluate the clinical outcomes after subsequent implantation of a new intrastromal corneal ring segment(ICRS)model followed by an additional short-arc ICRS implant in keratoconus patients.METHODS:This retrospective single-arm cohort study evaluated 25 eyes of 21 keratoconus patients implanted with the new ICRS followed by 140-arch length ICRS(140-ICRS)implantation.Uncorrected distance visual acuity(UDVA,logMAR),corrected distance visual acuity(CDVA,logMAR),sphere,astigmatism,keratometry,spherical equivalent(SE),and asphericity were compared preoperatively and postoperatively after both ICRS implantation.RESULTS:The average follow-up time after 140-ICRS implantation was 6.40±2.20mo.The mean preoperative UDVA improved from 1.27±0.14 preoperative to 0.52±0.26 after both ICRS implantation(P=0.03).The mean sphere value reduced from-5.34±2.74 preoperatively to-2.06±1.84 postoperatively(P<0.001)after the first ICRS implantation and decreased to-0.59±1.54 postoperatively(P<0.001)after 140-ICRS implantation.The mean preoperative astigmatism was-3.72±1.56 and improved to-2.82±1.08 after the first ICRS implantation,and following the 140-ICRS implantation,the mean astigmatism was-1.37±0.67(P=0.001).The SE and asphericity changes were statistically significant(P<0.001).The researchers did not find intraoperative or postoperative complications for both procedures.CONCLUSION:The combination of 2 different ICRSs can efficiently regularize the cornea,reduce the SE,and improve visual acuity in selected keratoconus patients.

Characteristics of corneal aberration in patients with bilateral keratoconus and unilateral corneal Vogt’s striae

AIM:To assess the corneal high-order aberration(HOA)and its correlation with corneal morphological parameters in patients with bilateral keratoconus(KCN)and unilateral Vogt’s striae.METHODS:A total of 168 eyes of 84 patients with KCN,whose corneas had definite signs of unilateral Vogt’s striae,were enrolled.Corneal HOA and morphological parameters were measured using Pentacam HR.RESULTS:The corneal morphological parameters between KCN eyes with and without Vogt’s striae were evidently different(P<0.001).The 3rd coma 90°,4th spherical aberration,5th coma 90°,root-mean-square(RMS)(total),and RMS(HOA)in the front,back surfaces and total cornea in KCN eyes with Vogt’s striae were significantly higher than those in KCN eyes without Vogt’s striae(P<0.001).In KCN eyes with Vogt’s striae,the 3rd coma 90°and 4th spherical aberration in the front surface and total cornea were negatively correlated with flat keratometry value(K1),steep keratometry value(K2),mean keratometry value(Km),maximum keratometry value(Kmax),anterior corneal elevation(ACE),and posterior corneal elevation(PCE;P<0.05).The 3rd coma 90°,4th spherical aberration in back surface and RMS(total),RMS(HOA)in the front,back surfaces,total cornea were positively correlated with K1,K2,Km,Kmax,ACE,and PCE(P<0.05).CONCLUSION:Corneal HOA especially vertical coma and spherical aberration may increase when Vogt’s striae appeared in KCN eyes.The scale of increase is significantly related with changes in corneal shapes.

Experimental Study of Corneal Innervation in Diabetic Mellitus

The morphology of corneal innervation was studied in rabbits with alloxan-induced diabetes.The experimental rabbits were killed after 6,8,10, 12weeks.Corneal innervation was studied by histochemical techniques and transimission electron microscopy.The results revealed that in diabetic rabbits,from 6 weeks,the density of nerve-nets was markedly sparser,the fibers were thinner and the activity of nerves was lower than those of the control group.Ultrastructural changes showed swelling of axons,irregular distribution of fibril and degeneration of mitochondria of varying degree.With the progress of disease the above changes were becoming more marked gradually.It may be assumed that these changes are related to hyperglycemia.

The Limbal Niche and Its Role in Maintaining Corneal Regeneration

In recent years, stem cells have been a focal point in research designed to evaluate the efficacy of ophthalmologic therapies, specifically those for corneal conditions. The corneal epithelium is one of the few regions of the body that maintains itself using a residual stem cell population within the adjacent limbus. Stem cell movement has additionally captivated the minds of researchers due to its potential application in different body regions. The cornea is a viable model for varying methods to track stem cell migratory patterns, such as lineage tracing and live imaging from the limbus. These developments have the potential to pave the way for future therapies designed to ensure the continuous regeneration of the corneal epithelium following injury via the limbal stem cell niche. This literature review aims to analyze the various methods of imaging used to understand the limbal stem cell niche and possible future directions that might be useful to consider for the better treatment and prevention of disorders of the cornea and corneal epithelium. .

Surgical approaches to correct corneal astigmatism at time of cataract surgery: a mini-review

Among refractive errors,astigmatism is the most common optical aberration,where refraction changes in different meridians of the eye.It causes blurred vision at any distance and includes corneal,lenticular,and retinal astigmatism.Cataract surgery used to cause a progressive increase in the pre-exisiting corneal astigmatism because of creating a surgically induced astigmatism,for example,a large size surgery incision.The development of surgical techniques during last decades has made cataract surgery interchange to treat preoperative corneal astigmatism at time of surgery.Nowadays,three surgical approaches can be used.By placing a sutureless clear corneal incision on the steep meridian of the cornea,a preoperative corneal astigmatism less than 1.0 D can be corrected.Single or paired peripheral corneal relaxing incisions(PCRIs)provide 1.0-3.0 D corneal astigmatism correction.PCRIs are typically used for treating 1.0-1.5 D of regular corneal astigmatism,if more than 2.0 D,the risk of overcorrection and irregular astigmatism is increased.When toric intraocular lenses(IOLs)are unavailable in markets,PCRIs are still a reasonable option for patients with up to 3.0 D of pre-existing corneal astigmatism.Toric IOLs implantation can correct 1.0-4.5 D of corneal astigmatism.Several IOLs are approved to correct a high degree of corneal astigmatism with cylinder power up to 12.0 D.These approaches can be used alone or in combination.

Thiel-Behnke Corneal Dystrophy in a Young Man in Denmark—A Case Report

Background: This case report presents a case of bilateral Thiel-Behnke corneal dystrophy in Denmark. Thiel-Behnke is an autosomal dominant inherited epithelial-stromal TGFBI dystrophy causing visual impairment. Methods and Results: This case study presents a 24-year-old Lithuanian man, with no previous ocular history, who had experienced slowly progressive visual impairment since his childhood. He was examined at the Department of Ophthalmology at Vejle Hospital and Aarhus University Hospital, where he was diagnosed with bilateral Thiel-Behnke corneal dystrophy. Histology confirmed the diagnosis. A lamellar corneal transplantation was performed in the right eye;however, due to epithelial growth under the corneal graft, it was later decided to redo the operation. Following the operations, the patient experienced a visual improvement in best corrected visual acuity (BCVA) from 0.1 (20/25 Snellen equivalent) to 0.3 (20/40 Snellen equivalent) in his right eye. Conclusions: This case of Thiel-Behnke corneal dystrophy is to our knowledge the first reported case in Denmark.

Adenomyosis uterine innervation in mice correlates to nerve growth factor expression,inflammation,and vascularization

BACKGROUND： Studies have shown that abnormal innervation is an important factor impacting occurrence and development of pathological pain in endometriosis. OBJECTIVE： To observe uterine innervation of adenomyosis mice and to analyze the cause of innervation changes due to nerve growth factor （NGF） expression, inflammation, and vascularization. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed at the Research Institute of Obstetrics and Gynecology Hospital, and Central Laboratory of Zhongshan Hospital, Fudan University from March to December 2008. MATERIALS： Tamoxifen was provided by Fudan Forward, China. Rabbit anti-mouse NGF was purchased from Santa Cruz Corporation, USA; rabbit anti-protein gene product 9.5 （PGP9.5） and rabbit anti-substance P （SP） were purchased from Chemicon, USA. METHODS： A total of 40 newborn ICR mice were randomly assigned to adenomyosis model and control groups, with 20 animals in each group. Mice in the adenomyosis model group were orally administrated 2.7 μmol/kg tamoxifen on days 2-5 after birth, while the controls were not treated. MAIN OUTCOME MEASURES： Both uteri from all mice were harvested at days 135-145 after birth Expressions of polyclonal PGP9.5 and SP were immunohistochemically detected to demonstrate pan- and sensory nerve fibers. Microvessel density was quantified in the endometrium and myometrium using immunochemical staining for polyclonal rabbit anti-CD31, which stained vessels. Gene expression for NGF, high-affinity tyrosine kinase receptor （trkA）, p75 neuretrophin receptor （p75NTR）, bradykinin receptor-1 （BKR-1）, and 2 （BKR-2）, as well as substance P receptor （neurokininl receptor, NK1-R）, were detected by reverse transcription-polymerase chain reaction. NGF-13 protein expression was detected by Western blot analysis. RESULTS： More nerve fibers were stained with PGP9.5 in the endometrium and myometrium, and with SP in the endometrium, in adenomyosis mice compared with controls （P 〈 0.01 and P 〈 0.05）. Microvessel density in the myometrium of adenomyosis mice was significantly greater than the controls （P 〈 0.01）. In the uterus of adenomyosis mice, mRNA expression of NGF and its two receptors （trkA and p75 NTR）, BKR-1, and NK1-R, as well as protein expression of NGF-β, were greater than the control mice （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Uterine innervation in the adenomyosis mice was increased compared with the controls. Moreover, NGF expression, inflammation, and vascularization, which have been shown to be impact factors of innervation, were abnormal in the uteri of adenomyosis mice.

Surgical anatomy of innervation of the gallbladder in humans and Suncus murinus with special reference to morphological understanding of gallstone formation after gastrectomy

AIM： To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.METHODS： The liver, gallbladder and surrounding structures were immersed in a 10 mg/L solution of alizarin red S in ethanol to stain the peripheral nerves in cadavers （n = 10）. Innervation in the areas was completely dissected under a binocular microscope. Similarly,innervation in the same areas of 10 Suncus murinus （S. murinus） was examined employing whole mount immunohistochemistry.RESULTS： Innervation of the gallbladder occurred predominantly through two routes. One was from the anterior hepatic plexus, the innervation occurred along the cystic arteries and duct. Invariably this route passed through the hepatoduodenal ligament. The other route was from the posterior hepatic plexus, the innervation occurred along the cystic duct ventrally. This route also passed through the hepatoduodenal ligament dorsally.Similar results were obtained in S. murinus.CONCLUSION： The route from the anterior hepatic plexus via the cystic artery and/or duct is crucial for preserving gallbladder innervation. Lymph node dissection specifically in the hepatoduodenal ligament may affect the incidence of gallstones after gastrectomy.Furthermore, the route from the posterior hepatic plexus via the common bile duct and the cystic duct to the gallbladder should not be disregarded. Preservation of the plexus may attenuate the incidence of gallstone formation after gastrectomy.

Osteoblasts are inherently programmed to repel sensory innervation

Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.

Role of intrahepatic innervation in regulating the activity of liver cells

Liver innervation comprises sympathetic,parasympathetic and peptidergic nerve fibers,organized as either afferent or efferent nerves with different origins and roles.Their anatomy and physiology have been studied in the past 30 years,with different results published over time.Hepatocytes are the main cell population of the liver,making up almost 80%of the total liver volume.The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and signaling pathways.In this short review,we have taken the task of condensing the most important data related to how the nervous system interacts with the liver and especially with the hepatocyte population,how it influences their metabolism and functions,and how different receptors and transmitters are involved in this complex process.

Does crossover innervation really affect the clinical outcome？ A comparison of outcome between unilateral and bilateral digital nerve repair

Digital nerve injuries are the mostly detected nerve injury in the upper extremity. However, since the clinical phenomenon of crossover innervation at some degree from uninjured digital nerve to the in- jured side occurs after digital nerve injuries is sustained, one could argue that this concept might even result in the overestimation of the outcome of the digital nerve repair. With this knowledge in mind, this study aimed to present novel, pure, focused and valuable clinical data by comparing the outcomes of bilateral and unilateral digital nerve repair. A retrospective review of 28 fingers with unilateral or bilateral digital nerve repair using end-to-end technique in 19 patients within 2 years was performed. Weber＇s two-point discrimination, sharp/dull discrimination, warm/cold sensation and Visual Analog Scale scoring were measured at final 12-month follow ups in all patients. There was no significant difference in recovery of sensibility after unilateral and bilateral digital nerve repairs. Though there is crossover innervation microscopically, it is not important in the clinical evaluation period. According to clinical findings from this study, crossover innervations appear to be negligible in the estimation of outcomes of digital neurorrhaphy.

Surgical anatomy of the innervation of pylorus in human and Suncus murinus, in relation to surgical technique for pylorus-preserving pancreaticoduodenectomy

AIM： To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS： The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of alizarin red S in ethanol to stain the peripheral nerves. The distribution details were studied to confirm innervations in the above areas using a binocular microscope. Similarly, innervations in 10 Suncus murinus were examined using the method of whole-mount imm unohistochemistry. RESULTS： The innervation of the pyloric region in humans involved three routes： One arose from the anterior hepatic plexus via the route of the suprapyloric/supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastroepiploic artery. For Suncus murinus, results similar to those in humans were observed. CONCLUSION： There are three routes of innervation of the pyloric region in humans, wherein the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy （PPPD）. However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries （the right gastroepiploic and gastroduodenal arteries）, and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD.

A paracrine role for white thermogenic adipocytes in innervation: an evidence-based hypothesis

White adipose tissue(WAT) stores energy and also plays an important endocrine role in producing adipokines for communication with the peripheral and central nervous system. WAT consists of the major lipogenic unilocular adipocytes and the minor populations of beige and brite multilocular adipocytes. These multilocular adipocytes express thermogenic genes and have phenotypic similarity with thermogenic brown adipose tissue. According to a current paradigm, multilocular adipocytes have a thermogenic function in WAT. In this mini review, we discuss data revealing heterogeneity among multilocular cell subsets in WAT and their functions beyond thermogenesis. We propose a hypothetical neuroendocrine role for multilocular adipocytes subsets in the formation of adaptive sensory-sympathetic circuits between the central nervous system and adipose tissue, which activate lipolysis and thermogenesis in WAT in high energy demand situations.

Regenerating nerve fiber innervation of extraocular muscles and motor functional changes following oculomotor nerve injuries at different sites

In the present study, the oculomotor nerves were sectioned at the proximal （subtentorial） and distal （superior orbital fissure） ends and repaired. After 24 weeks, vestibulo-ocular reflex evaluation confirmed that the regenerating nerve fibers following oculomotor nerve injury in the superior orbital fissure had a high level of specificity for innervating extraocular muscles. The level of functional recovery of extraocular muscles in rats in the superior orbital fissure injury group was remarkably superior over that in rats undergoing oculomotor nerve injuries at the proximal end （subtentorium）. Horseradish peroxidase retrograde tracing through the right superior rectus muscle showed that the distribution of neurons in the nucleus of the oculomotor nerve was directly associated with the injury site, and that crude fibers were badly damaged. The closer the site of injury of the oculomotor nerve was to the extraocular muscle, the better the recovery of neurological function was. The mechanism may be associated with the aberrant number of regenerated nerve fibers passing through the injury site.

Anatomical Evidence for the Neural Connection from the Emotional Brain to Autonomic Innervation in the Anterior Chamber Structures of the Eye

Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the anterior chamber(AC)structures might play an efferent role in the neural regulation of intraocular pressure(IOP).This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC.Methods A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein(PRV531)and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice,respectively.Fluorescent localization in the emotional brain and preganglionic nuclei was studied.Five and a half days after PRV531 injection into the right AC,fluorescent signals were observed in several emotional brain regions,including the amygdala,agranular insular cortex,lateral septal nuclei,periaqueductal gray,and hypothalamus.Autonomic preganglionic nuclei,including Edinger-Westphal nucleus,superior salivatory nucleus,and intermediolateral nucleus,were labeled using PRV531.Results The sensory trigeminal nuclei were not labeled using PRV531.The fluorescence signals in the nuclei mentioned above showed bilateral distribution,primarily on the ipsilateral side.Seven days after injecting FAST Dil into the AC,we observed no FAST Dil-labeled neurons in the central nervous system.Conclusion Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC,which provides anatomical support for the emotional influence of IOP via the ANS.

Research progress on animal models of corneal epithelial-stromal injury

A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring.Given the rising prevalence of blindness caused by corneal scarring,increasing attention has been focused on corneal epithelialstromal defects.Currently,the etiology and pathogenesis of these defects remain inadequately understood,necessitating further investigation through experimental research.Various modeling methods exist both domestically and internationally,each with distinct adaptive conditions,advantages,and disadvantages.This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury,including mechanical modeling,chemical alkali burns,post-refractive surgery infections,and genetic engineering.The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.