Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0595921 (
intraocular pressure
)
11,750
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To investigate the effect of E-64d, a selective inhibitor of calpain, on the expression of calpain and calpastatin in rat retina subject to ischemia/reperfusion injury (IRI). An animal model of retinal IRI was set up by increasing the
intraocular pressure
(110 mmHg) of a rat eye for 1 h. The retinal thickness and morphologic changes were detected by histology. The protein expression of
m-calpain
(a calpain isoform) in the retina was assessed by immunohistochemistry and Western blot assay. The mRNA of
m-calpain
as well as calpastatin (an endogenous protein inhibitor of calpain) in the retina was assessed by RT-PCR, and the ratio of
m-calpain
/calpastatin was then calculated. To evaluate the effect of E-64d on the expression of calpain, the drug (5 microl of 100 microM) was injected intravitreously immediately after IRI. There were retinal edematous changes, particularly in the inner plexiform layer after IRI. The protein expression of
m-calpain
in the retina was increased 24h after IRI, an effect that was inhibited by E-64d (P < 0.05). The mRNA expression of
m-calpain
and calpastatin was also increased 24 h and 3 h after IRI, respectively. Neither
m-calpain
nor calpastatin mRNA expression was influenced by E-64d (P > 0.05). The mRNA ratio of
m-calpain
to calpastatin was increased at the 6 h, 24 h and 72 h after IRI, and only at 24 h the increase of the ratio of
m-calpain
to calpastatin was inhibited by E-64d (P < 0.05). In the rat retina of IRI, E-64d inhibits the increase of
m-calpain
protein expression, as well as the mRNA ratio increase of
m-calpain
to calpastatin. E-64d also inhibited the retinal damage induced by IRI, suggesting a role for E-64d in the protection of the retinal apoptosis induced by IRI.
...
PMID:[Inhibition of calpain expression by E-64d in the rat retina subjected to ischemia/reperfusion injury]. 1861 Aug 34
Calpain has been shown to be involved in neurodegeneration, and in particular in retinal ganglion cell (RGC) death resulting from increased
intraocular pressure
(
IOP
) and ischemia. However, the specific roles of the two major calpain isoforms, calpain-1 and
calpain-2
, in RGC death have not been investigated. Here, we show that calpain-1 and
calpain-2
were sequentially activated in RGC dendrites after acute
IOP
elevation. By combining the use of a selective
calpain-2
inhibitor (C2I) and calpain-1 KO mice, we demonstrated that calpain-1 activity supported survival, while
calpain-2
activity promoted cell death of RGCs after
IOP
elevation. Calpain-1 activation cleaved PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) and activated the Akt pro-survival pathway, while
calpain-2
activation cleaved striatal-enriched protein tyrosine phosphatase (STEP) and activated STEP-mediated pro-death pathway in RGCs after
IOP
elevation. Systemic or intravitreal C2I injection to wild-type mice 2h after
IOP
elevation promoted RGC survival and improved visual function. Our data indicate that calpain-1 and
calpain-2
play opposite roles in high
IOP
-induced ischemic injury and that a selective
calpain-2
inhibitor could prevent acute glaucoma-induced RGC death and blindness.
...
PMID:Calpain-1 and calpain-2 play opposite roles in retinal ganglion cell degeneration induced by retinal ischemia/reperfusion injury. 2718 92
