Nitin Chitranshi

• Doctor of Philosophy
• Macquarie University

Glaucoma, a leading cause of irreversible blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs) and optic nerve damage, often associated with elevated intraocular pressure (IOP). Retinoid X receptors (RXRs) are ligand‐activated transcription factors crucial for neuroprotection, as they regulate gene expression to prom...

Neurodegenerative disorders, including Dementia, Parkinson's disease, various Vision disorders, Multiple sclerosis, and transsynaptic degenerative changes represent a significant challenge in aging populations. This editorial synthesizes and discusses recent advancements in understanding the genetic and environmental factors contributing to these d...

Neuropeptide Y (NPY), an endogenous peptide composed of 36 amino acids, has been investigated as a potential therapeutic agent for neurodegenerative diseases due to its neuroprotective attributes. This study investigated the neuroprotective effects of NPY in a mouse model of glaucoma characterized by elevated intraocular pressure (IOP) and progress...

The microtubule-associated protein Tau is a key player in various neurodegenerative conditions, including Alzheimer's disease (AD) and Tauopathies, where its hyperphosphorylation disrupts neuronal microtubular lattice stability. Glaucoma, a neurodegenerative disorder affecting the retina, leads to irreversible vision loss by damaging retinal gangli...

Aging is associated with progressive brain atrophy and declines in learning and memory, often attributed to hippocampal or cortical deterioration. The role of brain-derived neurotrophic factor (BDNF) in modulating the structural and functional changes in the brain and visual system, particularly in relation to BDNF Val66Met polymorphism, remains un...

Neural regeneration and neuroprotection represent strategies for future management of neurodegenerative disorders such as Alzheimer’s disease (AD) or glaucoma. However, the complex molecular mechanisms that are involved in neuroprotection are not clearly understood. A promising candidate that maintains neuroprotective signaling networks is neuroser...

Although researched extensively the understanding regarding mechanisms underlying glaucoma pathogenesis remains limited. Further, the exact mechanism behind neuronal death remains elusive. The role of neuroinflammation in retinal ganglion cell (RGC) death has been prominently theorised. This review provides a comprehensive summary of neuroinflammat...

Background Alzheimer’s disease (AD) is a neurodegenerative age‐dependent disorder which disrupts cognition and eventually leads to death. Neural regeneration and neuroprotection represent promising therapeutic approaches for AD. The predominantly neurally expressed serine protease inhibitor, neuroserpin, selectively inhibits plasminogen activators/...

Myelination of axons in the central nervous system offers numerous advantages, including decreased energy expenditure for signal transmission and enhanced signal speed. The myelin sheaths surrounding an axon consist of a multi-layered membrane that is formed by oligodendrocytes, while specific glycoproteins and lipids play various roles in this for...

Glaucoma is a common retinal disorder characterized by progressive optic nerve damage, resulting in visual impairment and potential blindness. Elevated intraocular pressure (IOP) is a major risk factor, but some patients still experience disease progression despite IOP-lowering treatments. Genome-wide association studies have linked variations in t...

Glaucoma is a complex multifactorial eye disease manifesting in retinal ganglion cell (RGC) death and optic nerve degeneration, ultimately causing irreversible vision loss. Research in recent years has significantly enhanced our understanding of RGC degenerative mechanisms in glaucoma. It is evident that high intraocular pressure (IOP) is not the o...

Glaucoma is a leading cause of permanent blindness worldwide and is characterized by neurodegeneration linked to progressive retinal ganglion cell (RGC) death, axonal damage, and neuroinflammation. Glutamate excitotoxicity mediated through N-methyl-D-aspartate (NMDA) receptors plays a crucial role in glaucomatous RGC loss. Sphingosine 1-phosphate r...

Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream e...

Sphingosine-1-phosphate receptor (S1PR) signaling regulates diverse pathophysiological processes in the central nervous system. The role of S1PR signaling in neurodegenerative conditions is still largely unidentified. Siponimod is a specific modulator of S1P1 and S1P5 receptors, an immunosuppressant drug for managing secondary progressive multiple...

Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease. In this meta-analysis, we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measu...

Our research has proved that the inhibitory activity of serine protease inhibitor neuroserpin (NS) is impaired due to its oxidation deactivation in glaucoma. Using genetic NS knockout (NS-/-) and NS overexpression (NS+/+Tg) animal models and antibody-based neutralisation approaches, we demonstrate that neuroserpin loss is detrimental to retinal str...

A large number of people worldwide suffer from visual impairment. However, most available therapies rely on impeding the development of a particular eye disorder. Therefore, there is an increasing demand for effective alternative treatments, specifically regenerative therapies. Extracellular vesicles, including exosomes, ectosomes, or microvesicles...

Purpose: Recent studies have shown neuroserpin (NS) plays a critical role in several neurodegenerative diseases. The neuroprotective role of NS administration in the retina has been reported in an ischemic/reperfusion mouse model of glaucoma. Here, we studied the effect of neuroserpin loss on retinal integrity in normal and experimental glaucoma co...

Purpose: To investigate the relationship between the APOE (Apolipoprotein ε4) allele and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on retinal structural and vascular characteristics in healthy aging subjects. Methods: 109 healthy participants (mean age 67.1 (±9.0) years) were recruited. Participants were classified as either AP...

Purpose: Retinal ganglion cell (RGC) degeneration and visual field loss are distinctive features of primary open angle glaucoma. Similar pathologies have been observed in Alzheimer's Disease patients, concomitant to amyloid-β aggregation. Here, we investigated the effect of amyloid precursor protein (APP) modulation in the retina and examined the p...

Glaucoma is a complex neurodegenerative disease characterized by optic nerve damage and apoptotic retinal ganglion cell (RGC) death, and is the leading cause of irreversible blindness worldwide. Among the sphingosine 1‐phosphate receptors (S1PRs) family, S1PR1 is a highly expressed subtype in the central nervous system and has gained rapid attentio...

Neuropeptide Y (NPY), a sympathetic neurotransmitter, is involved in various physiological functions, and its dysregulation is implicated in several neurodegenerative diseases. Glutamate excitotoxicity, endoplasmic reticulum (ER) stress, and oxidative stress are the common mechanisms associated with numerous neurodegenerative illnesses. The present...

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can pene...

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug...

To examine the relationships of retinal structural (optical coherence tomography) and visual functional (multifocal visual evoked potentials, mfVEP) indices with neuropsychological and brain structural measurements in healthy older subjects. 95 participants (mean (SD) age 68.1 (9.0)) years were recruited in the Optic Nerve Decline and Cognitive Cha...

Retinoid X receptors (RXRs) present a subgroup of the nuclear receptor superfamily with particularly high evolutionary conservation of ligand binding domain. The receptor exists in α, β, and γ isotypes that form homo-/heterodimeric complexes with other permissive and non-permissive receptors. While research has identified the biochemical roles of s...

Alzheimer’s disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems w...

Neuroserpin is an axonally secreted serpin that is involved in regulating plasminogen and its enzyme activators, such as tissue plasminogen activator (tPA). The protein has been increasingly shown to play key roles in neuronal development, plasticity, maturation and synaptic refinement. The proteinase inhibitor may function both independently and t...

Glaucoma is an age-related neurodegenerative disorder characterized by retinal ganglion cell (RGC) degeneration and excavation of the optic nerve head (ONH). It is associated with an increase in intraocular pressure (IOP) and progressive decline in the visual field. Reduction in the retrograde axonal transport of neurotrophic factors such as brain-...

Alterations in the nuclear retinoid X receptor (RXRs) signalling have been implicated in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, stroke, multiple sclerosis and glaucoma. Single nucleotide polymorphisms (SNPs) are the main cause underlying single nucleic acid variations which in turn determine heterogeneity with...

Liquid self-nanoemulsifying drug delivery system (L-SNEDDS) of curcumin and quercetin were prepared by dissolving them in isotropic mixture of Labrafil M1944CS®, Capmul MCM®, Tween-80® and Transcutol P®. The prepared L-SNEDDS were solidified using Ganoderma lucidum extract, probiotics and Aerosil-200® using spray drying. These were further converte...

Cannabis (Cannabis sativa), popularly known as marijuana, is the most commonly used psychoactive substance and is considered illicit in most countries worldwide. However, a growing body of research has provided evidence of the therapeutic properties of chemical components of cannabis known as cannabinoids against several diseases including Alzheime...

Alzheimer's disease (AD) is the leading cause of dementia that has remained a major medical, sociocultural and economical challenge globally. Previously developed treatments like anticholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate receptor (NMDAR) antagonists only provide short-term symptomatic improvement and do not prevent progression...

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspe...

There is a strong interrelationship between eye and brain diseases. It has been shown that neurodegenerative changes can spread bidirectionally in the visual pathway along neuronal projections; for example, damage to retinal ganglion cells in the retina leads to degeneration of the visual cortex (anterograde degeneration) and vice versa (retrograde...

Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment st...

Mitochondrial dysfunction is involved in Alzheimer’s disease (AD) pathogenesis. Mitochondria have their own genetic material; however, most of their proteins (∼99%) are synthesized as precursors on cytosolic ribosomes, and then imported into the mitochondria. Therefore, exploring proteome changes in these organelles can yield valuable information a...

SH2 domain containing tyrosine phosphatase 2 (Shp2; PTPN11) regulates several intracellular pathways downstream of multiple growth factor receptors. Our studies implicate that Shp2 interacts with Caveolin-1 (Cav-1) protein in retinal ganglion cells (RGCs) and negatively regulates BDNF/TrkB signaling. This study aimed to investigate the mechanisms u...

Different parts of the brain are affected distinctively in various stages of the Alzheimer's disease (AD) pathogenesis. Identifying the biochemical changes in specific brain regions is key to comprehend the neuropathological mechanisms in early pre‐symptomatic phases of AD. Quantitative proteomics profiling of four distinct areas of the brain of yo...

Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, and ca...

Background Human and animal studies demonstrate that both amyloid precursor protein and phosphorylated Tau which are hallmark proteins associated with Alzheimer’s disease (AD) pathology are perturbed in the retinal tissues. The accumulation of pTau in the retina in addition to the brain tissue suggests eye as a valuable structure for disease diagno...

Background The microtubule associated protein tau is known to have several important functions like assembly and stabilisation of microtubules, axonal transport and neurite outgrowth in neurodegenerative diseases. Gsk3β, glycogen synthase kinase, plays a key role in regulating tau protein activity. There is little understanding of tau and Gsk3β ass...

Introduction: Diabetic retinopathy (DR) is associated with damage to the retinal blood vessels that lead eventually to vision loss. The existing treatments of DR are invasive, expensive, and cumbersome. To overcome challenges associated with existing therapies, various intraocular sustained release and novel drug delivery systems (NDDS) have been e...

Introduction: Diabetic retinopathy (DR) is associated with damage to the retinal blood vessels that lead eventually to vision loss. The existing treatments of DR are invasive, expensive, and cumbersome. To overcome challenges associated with existing therapies, various intraocular sustained release and novel drug delivery systems (NDDS) have been e...

Retinal ganglion cell degeneration is a characteristic feature of glaucoma, and accordingly, protection of these cells constitutes a major therapeutic objective in the disease. Here, we demonstrate the key influence of caveolin (Cav) in regulating the inner retinal homeostasis in two models of experimentally elevated intraocular pressure (IOP). Two...

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected...

The objective of study was to develop modified apple polysaccharide (MAP) based silver nanoparticles (AgNPs) loaded with mesalamine (MES) for effective treatment of ulcerative colitis in acetic acid induced rat model. AgNPs were prepared by reducing silver nitrate using MAP solution. The size and zeta potential of AgNPs was 89 ± 3 nm and -16.3± 1.5...

Current evidence suggests that exposure to chronically induced intraocular pressure (IOP) leads to neurodegenerative changes in the inner retina. This study aimed to determine retinal proteomic alterations in a rat model of glaucoma and compared findings with human retinal proteomics changes in glaucoma reported previously. We developed an experime...

Background: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection...

Current evidence suggests that exposure to chronically induced intraocular pressure (IOP) leads to neurodegenerative changes in the inner retina. This study aimed to determine retinal proteomic alterations in a rat model of glaucoma and compared findings with human retinal proteomics changes in glaucoma reported previously. We developed an experime...

Background: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of this century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide with over 200,000 fatalities having already occurred by mid-April 2020, and the infection r...

Background: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection r...

Cell cycle dysregulation has been implicated in the pathogenesis of neurodegenerative disorders. Specialised function obligates neuronal cells to subsist in a quiescent state of cell cycle once differentiated and therefore the circumstances and mechanisms underlying aberrant cell cycle activation in post-mitotic neurons in physiological and disease...

Increased amyloid β (Aβ) aggregation is a hallmark feature of Alzheimer’s disease (AD) pathology. The APP/PS1 mouse model of AD exhibits accumulation of Aβ in the retina and demonstrates reduced retinal function and other degenerative changes. The overall molecular effects of AD pathology on the retina remain undetermined. Using a proteomics approa...

Retinoid X receptors (RXRs) play an important role in transcription, are involved in numerous cellular networks from cell proliferation to lipid metabolism and are essential for normal eye development. RXRs form homo or heterodimers with other nuclear receptors, bind to DNA response elements and regulate several biological processes including neuro...

Purpose: To investigate whether the brain-derived neurotrophic factor (BDNF) Val66Met genotype is associated with the rate of progression of open-angle glaucoma (OAG). Methods: In this retrospective cohort study, 148 OAG patients (292 eyes) were enrolled with a median follow-up period of 5.3 (range, 1.1-8.6) years. All participants had undergone...

Amyloid β (Aβ) accumulation and its aggregation is characteristic molecular feature of the development of Alzheimer’s disease (AD). More recently, Aβ has been suggested to be associated with retinal pathology associated with AD, glaucoma and drusen deposits in age related macular degeneration (AMD). In this study, we investigated the proteins and b...

Retinoid X receptors (RXRs) belong to the nuclear receptor superfamily, and upon ligand activation, these receptors control gene transcription via either homodimerization with themselves or heterodimerization with the partner‐nuclear receptor. The protective effects of RXRs and RXR agonists have been reported in several neurodegenerative diseases,...

The spread of neurodegeneration through the human brain network is reported as underlying the progression of neurodegenerative disorders. However, the exact mechanisms remain unknown. The human visual pathway is characterized by its unique hierarchical architecture and, therefore, represents an ideal model to study trans-synaptic degeneration, in c...

Retinoid X-receptors (RXRs) are members of the ligand-dependent transcription factor family of nuclear receptors that have gained recent research focus as potential targets for neurodegenerative disorders. Bexarotene is an RXR pharmacological agonist that is shown to be neuroprotective through its effects in promoting amyloid beta (Aβ) uptake by th...

Glaucoma is characterized by the loss of retinal ganglion cells (RGC), and accordingly the preservation of RGCs and their axons has recently attracted significant attention to improve therapeutic outcomes in the disease. Here, we report that Src homology region 2-containing protein tyrosine phosphatase 2 (Shp2) undergoes activation in the RGCs, in...

Purpose: To assess differential patterns of axonal loss and demyelination in the optic nerve in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Design: Cross-sectional study. Participants: One hundred ninety-two participants, including 136 MS patients (272 eyes), 19 NMOSD patients (38 eyes), and 37 healthy control...

Background: Retinal ganglion cell (RGC) degeneration is a major feature of glaucoma pathology. Neuroprotective approaches that delay or halt the progression of RGC loss are needed to prevent vision loss which can occur even after conventional medical or surgical treatments to lower intraocular pressure. Objective: The aim of this review was to e...

SH2 domain-containing tyrosine phosphatase-2 (PTPN11 or Shp2) is a ubiquitously expressed protein that plays a key regulatory role in cell proliferation, differentiation and growth factor (GF) signaling. This enzyme is well expressed in various retinal neurons and has emerged as an important player in regulating survival signaling networks in the n...

Neuroserpin is a serine protease inhibitor that regulates the activity of plasmin and its activators in the neuronal tissues. This study provides novel evidence of regulatory effect of the neuroserpin on plasmin proteolytic activity in the retina in glaucoma. Human retinal and vitreous tissues from control and glaucoma subjects as well as retinas f...

Abstarct Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed...

PTPN11 is associated with regulation of growth factor signalling pathways in neuronal cells. Using SH-SY5Y neuroblastoma cells, we showed that adeno-associated virus (AAV) mediated PTPN11 upregulation was associated with TrkB antagonism, reduced neuritogenesis and enhanced endoplasmic reticulum (ER) stress response leading to apoptotic changes. Gen...

Accumulation of amyloid β (Aβ) and its aggregates in the ageing central nervous system is regarded synonymous to Alzheimer's disease (AD) pathology. Despite unquestionable advances in mechanistic and diagnostic aspects of the disease understanding, the primary cause of Aβ accumulation as well as its in vivo roles remains elusive; nonetheless, the m...

The caveolin (Cav) family of proteins comprises key constituents of caveolar structures in cell membranes, which are involved in receptor-independent endocytosis and cellular signalling pathways. Three isoforms of caveolin viz. cav-1, cav-2 and cav-3 encoded by CAV1, CAV2 and CAV3 genes respectively, have been reported to be expressed in various ti...

The APP-PS1δE9 mouse model of Alzheimer's disease (AD) exhibits age dependent amyloid β (Aβ) plaque formation in their central nervous system due to high expression of mutated human APP and PSEN1 transgenes. Here we evaluated Aβ deposition and changes in soluble Aβ accumulation in the retinas of aged APP-PS1 mice using a combination of immunofluore...

TrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signaling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mecha...

7,8-dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEG...

The visual evoked potential (VEP) recording is widely used in clinical practice to assess the severity of optic neuritis in its acute phase, and to monitor the disease course in the follow-up period. Changes in the VEP parameters closely correlate with pathological damage in the optic nerve. This protocol provides a detailed description about the r...

Abnormal amyloid precursor protein (APP) expression and amyloid β (Aβ) deposition have been shown to be involved in the development of retinal ganglion cell apoptosis in glaucoma. The APP-PS1 mouse model of Alzheimer’s disease (AD) expresses several fold higher mutated human APP and PSEN1 transgenes compared to the endogenous murine APP. These mice...

Abstract Purpose Isofluorane has been widely used for recovery experiments, including visual electrophysiological studies, in rodents. However, it can potentially affect visual evoked potential (VEP) recordings due to GABAergic activity associated with it and subsequent burst suppression on the electroencephalogram response. This study aims to in...

Bleomycin a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. It is used as an antineoplastic and inhibits the DNA metabolism of the solid tumors.

Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions. The genetic architecture of microbe may bear a significant signature not only in the sequences position, but also in the lifestyle to which it is adapted. It becomes a challenge for the society to find new chemical entities wh...

The accuracy of ligand-protein docking may be affected by the presence of water molecules on the surface of proteins. Water can form complex bridging networks and can play a critical role in dictating the binding mode of ligands. A recent analysis of high-resolution crystal structures of ligand-protein complexes revealed that 85% of the complexes h...

Aim: Recent genome-wide association studies have revealed large numbers of single nucleotide polymorphisms (SNPs) related to Alzheimer’s disease. Here, we have investigated the gene CTSB, which plays a crucial role in encoding CTSB, a lysosomal cysteine proteinase protein. CTSB is also involved in the proteolytic processing of amyloid precursor pro...

The identification of important chemical features of acetylcholinesterase (AChE) inhibitors will be helpful to discover the potent candidate to inhibit the AChE activity. The best hypothesis from structure-based, Hypo1, one hydrophobic (H) pointed toward ILE444, TRP84, three hydrogen bond accepter (HBA), two hydrogen bond donor, one positive ioniza...

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by progressive motor deficits, psychiatric deterioration, worsening chorea, cognitive impairment due to neuronal cell loss in the basal ganglia, cerebral cortex, and its fragments interactions with themselves and other biomolecules that results in aggregate...