369 research outputs found
Ocular transient receptor potential channel function in health and disease
Transient receptor potential (TRP) channels sense and transduce environmental
stimuli into Ca2+ transients that in turn induce responses essential for cell
function and adaptation. These non-selective channels with variable Ca2+
selectivity are grouped into seven different subfamilies containing 28
subtypes based on differences in amino acid sequence homology. Many of these
subtypes are expressed in the eye on both neuronal and non-neuronal cells
where they affect a host of stress-induced regulatory responses essential for
normal vision maintenance. This article reviews our current knowledge about
the expression, function and regulation of TRPs in different eye tissues. We
also describe how under certain conditions TRP activation can induce responses
that are maladaptive to ocular function. Furthermore, the possibility of an
association between TRP mutations and disease is considered. These findings
contribute to evidence suggesting that drug targeting TRP channels may be of
therapeutic benefit in a clinical setting. We point out issues that must be
more extensively addressed before it will be possible to decide with certainty
that this is a realistic endeavor. Another possible upshot of future studies
is that disease process progression can be better evaluated by profiling
changes in tissue specific functional TRP subtype activity as well as their
gene and protein expression
L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic- Induced Shrinkage through Interacting with TRPV1 Channels
Background/Aims: Ocular surface health depends on conjunctival epithelial
(HCjE) layer integrity since it protects against pathogenic infiltration and
contributes to tissue hydration maintenance. As the same increases in tear
film hyperosmolarity described in dry eye disease can increase corneal
epithelial transient receptor potential vanilloid type-1 (TRPV1) channel
activity, we evaluated its involvement in mediating an osmoprotective effect
by L-carnitine against such stress. Methods: Using siRNA gene silencing,
Ca2+imaging, planar patch- clamping and relative cell volume measurements, we
determined if the protective effects of this osmolyte stem from its
interaction with TRPV1. Results: TRPV1 activation by capsaicin (CAP) and an
increase in osmolarity to≈450 mOsM both induced increases in Ca2+levels. In
contrast, blocking TRPV1 activation with capsazepine (CPZ) fully reversed this
response. Similarly, L-carnitine (1 mM) also reduced underlying whole-cell
currents. In calcein-AM loaded cells, hypertonic-induced relative cell volume
shrinkage was fully blocked during exposure to L-carnitine. On the other hand,
in TRPV1 gene-silenced cells, this protective effect by L-carnitine was
obviated. Conclusion: The described L-carnitine osmoprotective effect is
elicited through suppression of hypertonic-induced TRPV1 activation leading to
increases in L-carnitine uptake through a described Na+-dependent L-carnitine
transporter
Anti-inflammatory and combined antiinflammatory/ analgesic medication in the early management of iliotibial band friction syndrome A clinical trial
Forty-three athletes presenting with unilateral iliotibial band friction syndrome (ITBFS) were randomly divided into three groups for the first 7 days of treatment (placebo-controlled, double-blind): 1 - placebo (N = 13); 2 - anti-inflammatory medication (N = 14) (Voharen; Geigy); and 3 - analgesicl anti-inflammatory combined medication (N =. 16) (Myprodol; Rio Ethicals). All subjects rested from day 0 to day 7 and all groups received the same physiotherapy outpatient treatment programme from day 3 to day 7. On days 0, 3 and 7 the subjects performed a functional treadmill running test (maximum 30 minutes) during which they reported pain (scale 0-10; 0 = no pain, 10 = unbearable pain) each minute. Total running distance, total running time and the area under the pain v. time curve was calculated. Daily 24-hour recall pain scores were also recorded. The 24-hour recall pain scores decreased significantly for all the groups over the treatment period. This method of assessing efficacy of treatment therefore failed to show differences between groups. In contrast, during the running test only group 3 improved their total running time and distance from day 0 to day 7, whereas in all the groups the area under the pain v. time curve decreased from day 0 to day 7. All the other groups improved total running time and running distance from day 3 to day 7. All three treatment modalities are effective in the early. treatment of ITBFS but physiotherapy in combination with analgesicl anti-inflammatory medication is superior. A functional running test, which is more sensitive than conventional pain-recall· methods in assessing efficacy of treatment in this type of clinical trial, is described
Temperature-Sensitive Transient Receptor Potential Channels in Corneal Tissue Layers and Cells
We here provide a brief summary of the characteristics of transient receptor potential channels (TRPs) identified in corneal tissue layers and cells. In general, TRPs are nonselective cation channels which are Ca ²⁺ permeable. Most TRPs serve as thermosensitive molecular sensors (thermo-TRPs). Based on their functional importance, the possibilities are described for drug-targeting TRP activity in a clinical setting. TRPs are expressed in various tissues of the eye including both human corneal epithelial and endothelial layers as well as stromal fibroblasts and stromal nerve fibers. TRP vanilloid type 1 (TRPV1) heat receptor, also known as capsaicin receptor, along with TRP melastatin type 8 (TRPM8) cold receptor, which is also known as menthol receptor, are prototypes of the thermo-TRP family. The TRPV1 functional channel is the most investigated TRP channel in these tissues, owing to its contribution to maintaining tissue homeostasis as well as eliciting wound healing responses to injury. Other thermo-TRP family members identified in these tissues are TRPV2, 3 and 4. Finally, there is the TRP ankyrin type 1 (TRPA1) cold receptor. All of these thermo-TRPs can be activated within specific temperature ranges and transduce such inputs into chemical and electrical signals. Although several recent studies have begun to unravel complex roles for thermo-TRPs such as TRPV1 in corneal layers and resident cells, additional studies are needed to further elucidate their roles in health and disease
L-carnitine suppresses transient receptor potential vanilloid type 1 activity and myofibroblast transdifferentiation in human corneal keratocytes
Corneal stromal wound healing is a well-balanced process promoted by overlapping phases including keratocyte proliferation, inflammatory-related events, and tissue remodeling. L-carnitine as a natural antioxidant has shown potential to reduce stromal fibrosis, yet the underlying pathway is still unknown. Since transient receptor potential vanilloid 1 (TRPV1) is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing, we investigated if L-carnitine can mediate inhibition of the fibrotic response through suppression of TRPV1 activation in human corneal keratocytes (HCK). We determined TRPV1-induced intracellular calcium transients using fluorescence calcium imaging, channel currents by planar patch-clamping, and cell migration by scratch assay for wound healing. The potential L-carnitine effect on TRPV1-induced myofibroblast transdifferentiation was evaluated by immunocytochemical detection of alpha smooth muscle actin. RT-PCR analysis confirmed TRPV1 mRNA expression in HCK. L-carnitine (1 mmol/l) inhibited either capsaicin (CAP) (10 µmol/l), hypertonic stress (450 mOsmol/l), or thermal increase (>43 °C) induced Ca2+ transients and corresponding increases in TRPV1-induced inward and outward whole-cell currents. This was accompanied by suppression of injury-induced increases in myofibroblast transdifferentiation and cell migration. In conclusion, L-carnitine contributes to inhibit stromal scarring through suppressing an injury-induced intrinsic TRPV1 activity that is linked with induction of myofibroblast transdifferentiation in HCK cells
On “The Analysis of Ranked Data Derived from Completely Randomized Factorial Designs”
Extensions of the Kruskal-Wallis procedure for a factorial design are reviewed and researched under various degrees and kinds of nonnullity. It was found that the distributions of these test statistics are a Function of effects other than those being tested except under the completely null situation and their use is discouraged.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
TRPV4 Stimulation Level Regulates Ca2+-Dependent Control of Human Corneal Endothelial Cell Viability and Survival
The functional contribution of transient receptor potential vanilloid 4 (TRPV4) expression in maintaining human corneal endothelial cells (HCEC) homeostasis is unclear. Accordingly, we determined the effects of TRPV4 gene and protein overexpression on responses modulating the viability and survival of HCEC. Q-PCR, Western blot, FACS analyses and fluorescence single-cell calcium imaging confirmed TRPV4 gene and protein overexpression in lentivirally transduced 12V4 cells derived from their parent HCEC-12 line. Although TRPV4 overexpression did not alter the baseline transendothelial electrical resistance (TEER), its cellular capacitance (Ccl) was larger than that in its parent. Scanning electron microscopy revealed that only the 12V4 cells developed densely packed villus-like protrusions. Stimulation of TRPV4 activity with GSK1016790A (GSK101, 10 mu mol/L) induced larger Ca2+ transients in the 12V4 cells than those in the parental HCEC-12. One to ten nmol/L GSK101 decreased 12V4 viability, increased cell death rates and reduced the TEER, whereas 1 mu mol/L GSK101 was required to induce similar effects in the HCEC-12. However, the TRPV4 channel blocker RN1734 (1 to 30 mu mol/L) failed to alter HCEC-12 and 12V4 morphology, cell viability and metabolic activity. Taken together, TRPV4 overexpression altered both the HCEC morphology and markedly lowered the GSK101 dosages required to stimulate its channel activity
- …