1 ght into the possible biological function of
myocilin.
2 Grp94 and reducing its novel client, mutant
myocilin.
3 uced expression of wild type, Q368X or P370L
myocilin.
4 M citrate synthase in the presence of 650 nM
myocilin.
5 -like receptors, immunoglobulins, and mutant
myocilin.
6 tions in other OLF family members, including
myocilin.
7 s to promote the clearance of toxic forms of
myocilin.
8 n anterior chamber exchange with recombinant
myocilin (
2 microg/mL), whereas the fellow eye received
9 Myocilin,
a causative gene for open angle glaucoma, enco
10 promotes the aggregation of mutant forms of
myocilin,
a protein associated with primary open-angle g
11 Mutant
myocilin accumulates in the endoplasmic reticulum for un
12 Tg-MYOC(Y437H) mice, most likely by reducing
myocilin accumulation and ER stress in the TM.
13 proved the secretion of myocilin and reduced
myocilin accumulation as well as endoplasmic reticulum (
14 s, suggesting broader relevance of misfolded
myocilin across the disease spectrum, but the absence of
15 aken together, the interaction of Grp94 with
myocilin aggregates can be manipulated by cellular envir
16 the toxic accumulation of amyloid-containing
myocilin aggregates, hastening the onset of the prevalen
17 Myocilin also affects differentiation of oligodendrocyte
18 Recombinant
myocilin also increased outflow resistance in eyes incub
19 Myocilin also protected GAPDH from thermal inactivation
20 Myocilin also stimulated osteogenic differentiation of w
21 Myocilin also suppresses the thermal aggregation of citr
22 iency virus vector encoding both full-length
myocilin (
amino acids 1-503 fused to C-terminal V5 and s
23 orescence (EF) microscopy with antibodies to
myocilin and alpha smooth muscle (alpha-SMA).
24 as performed in addition to Western blots of
myocilin and alphaB-crystallin.
25 Myocilin and angiopoietin-like 7 expression in response
26 ed by the synergistic interaction of mutated
myocilin and another significant risk factor, oxidative
27 Immunohistochemistry was performed with anti-
myocilin and anti-V5 antibodies.
28 ar meshwork cells differently from wild-type
myocilin and can reduce cell survival.
29 duced reporter gene luciferase or endogenous
myocilin and fibronectin expression were determined.
30 2 interacted with Olfm1 and -3, but not with
myocilin and gliomedin.
31 Treatment of NIH 3T3 cells with
myocilin and its fragments induced intracellular redistr
32 The exact role of
myocilin and its functional association with glaucoma ar
33 To study the functions of human
myocilin and its two proteolytic fragments, these protei
34 Myocilin and optineurin are two genes linked to glaucoma
35 ects of force-expressed wild-type and mutant
myocilin and optineurin on neurite outgrowth in neuronal
36 ells with pEGFP-N1 (mock control) as well as
myocilin and optineurin plasmids including pMYOC(WT)-EGF
37 pOPTN(WT)-EGFP and pOPTN(E50K)-EGFP nor the
myocilin and optineurin small-interfering RNA treatments
38 ts demonstrated that the two glaucoma genes,
myocilin and optineurin, exhibited differential effects
39 PBA significantly improved the secretion of
myocilin and reduced myocilin accumulation as well as en
40 Myocilin and the heparin II domain of fibronectin also i
41 , gain-of-function association between human
myocilin and the peroxisomal targeting signal type 1 rec
42 used to determine the protein expression of
myocilin and TIMP-1 in conditioned media collected from
43 Quantitative PCR for
myocilin and versican isoforms was performed in addition
44 Myocilin and Wnt proteins may perform redundant function
45 actomedin 1 (Olfm1), olfactomedin 3 (Olfm3),
myocilin,
and gliomedin was studied by using co-immunopr
46 beta-galactosidase (TAT-HA-beta-gal), TAT-HA-
myocilin,
and TAT-HA-myocilin-EGFP.
47 in structure, function, and pathogenesis for
myocilin;
and offers insights into highly conserved, bio
48 eted protein, acidic, cysteine rich (SPARC),
myocilin,
angiopoietin-like factor (ANGPTL)-7, and trans
49 Mutated
myocilin appears to affect trabecular meshwork cells dif
50 Recombinant
myocilin appears to form a complex in porcine aqueous hu
51 Recombinant
myocilin appears to form a complex in porcine aqueous hu
52 Functions of
myocilin are poorly understood.
53 However, the functions of wild-type
myocilin are still not well understood.
54 f myocilin was blocked by antibodies against
myocilin,
as well as secreted inhibitors of Wnt signalin
55 cues glaucoma phenotypes in a mouse model of
myocilin-
associated glaucoma (Tg-MYOC(Y437H) mice).
56 Our results indicate that
myocilin-
associated glaucoma is an ER storage disease an
57 it these interactions as a strategy to treat
myocilin-
associated glaucoma.
58 Myocilin at 18 nM was more effective than 1 muM bovine s
59 phin-associated protein complex (DAPC), as a
myocilin-
binding candidate.
60 Myocilin binds to ErbB2/ErbB3, activates these receptors
61 scientists using the wrong methods to study
myocilin biology?
62 f efficiently handling the removal of mutant
myocilin,
but when Grp94 is depleted, degradation of mut
63 Induction of
myocilin by dexamethasone was observed in conditioned me
64 ed protein (Grp) 94 depletion reduces mutant
myocilin by engaging autophagy.
65 Studies were conducted to see whether
myocilin can act as a general molecular chaperone.
66 The Y437H mutant
myocilin cell line also produced more reactive oxygen sp
67 The Y437H mutant
myocilin cell line showed the highest sensitivity to the
68 enes were down-regulated in the Y437H mutant
myocilin cell line, but not in other cell lines.
69 ), but their co-aggregation precludes mutant
myocilin clearance by ER-associated degradation.
70 mide gel electrophoresis was used to analyze
myocilin complex formation in porcine aqueous humor.
71 urite length in those cells transfected with
myocilin constructs was shortened and the number of neur
72 Myocilin-
containing conditioned medium also increased pr
73 We further determined whether
myocilin contributes to GC-OHT.
74 Thus, strategies aimed at eliminating
myocilin could be therapeutically relevant for glaucoma.
75 In addition,
myocilin-
deficient mesenchymal stem cells exhibited redu
76 Grp94-selective inhibitor facilitated mutant
myocilin degradation and rescued phenotypes in a transge
77 metastasis model as well as enhanced mutant
myocilin degradation in a glaucoma model compared to BnI
78 oss the disease spectrum, but the absence of
myocilin does not cause disease.
79 T in humans, and we further demonstrate that
myocilin does not play a major role in DEX-induced OHT i
80 Transduction of myocilin or
myocilin-
EGFP was evaluated by immunostaining or fluores
81 AT-HA-beta-gal), TAT-HA-myocilin, and TAT-HA-
myocilin-
EGFP.
82 Levels of extracellular
myocilin expressed by TM cells were increased in respons
83 Full-length mutant
myocilin expressed in mammalian cells forms intracellula
84 nd compared gene expression profiles between
myocilin-
expressing and vector control cell lines by a m
85 e) polymerase, were significantly reduced in
myocilin-
expressing cells as compared with control cells
86 eam kinases, c-Raf and MEK, was increased in
myocilin-
expressing cells compared with control cells.
87 raction of differentially expressed genes in
myocilin-
expressing cells was associated with cell growt
88 Increased proliferation of
myocilin-
expressing cells was demonstrated by the WST-1
89 Myocilin-
expressing cells were more resistant to serum s
90 Conditioned medium from
myocilin-
expressing cells, as well as purified myocilin,
91 ascorbic acid to DMEM-AH failed to increase
myocilin expression beyond that obtained with DMEM-AH.
92 Dex-induced
myocilin expression had both cytosolic and extracellular
93 CR analysis revealed significant decrease in
myocilin expression in eyes receiving AA compared to nai
94 Wild-type mice showed increased
myocilin expression in the TM on DEX-Ac treatment.
95 GC-induced
myocilin expression in the trabecular meshwork (TM) has
96 In vitro quantitative assays of
myocilin expression in TM cells can be used for characte
97 The
myocilin expression is known to be up-regulated by gluco
98 eutic doses of BOL-303242-X elicit a reduced
myocilin expression profile in TM cells by virtue of the
99 Myocilin expression was also analyzed by Western immunob
100 In DMEM-AH-conditioned medium,
myocilin expression was increased and TIMP-1 expression
101 Myocilin expression was investigated in a subset of eyes
102 cross-linked actin networks and induction of
myocilin expression.
103 h human MSCs exhibiting the highest level of
myocilin expression.
104 rpose of this investigation was to elucidate
myocilin function(s).
105 nto adipocytes, and treatment with exogenous
myocilin further enhanced osteogenesis.
106 Mutations in the
myocilin gene (MYOC) are the most common known genetic c
107 The
myocilin gene (MYOC) is the most common glaucoma-causing
108 Mutations in the
myocilin gene are associated with juvenile and adult-ons
109 human pathology related to mutations in the
MYOCILIN gene is primary open-angle glaucoma.
110 It is well documented that mutations in the
MYOCILIN gene may lead to juvenile- and adult-onset prim
111 Mutations in the
MYOCILIN gene may lead to juvenile- and adult-onset prim
112 and referred by their eye practitioner, and
Myocilin genetic testing was performed by direct sequenc
113 The levels of wild type and mutant
myocilin-
GFP in various clones were confirmed by Western
114 ressing wild type or mutant (Q368X or P370L)
myocilin-
GFP upon Dox induction, are valuable in facilit
115 high expression of wild type, Q368X or P370L
myocilin-
GFP upon doxycycline (Dox) induction were obtai
116 al for patients suffering from some cases of
myocilin glaucoma.
117 Expression of human
myocilin glaucomatous mutations in mouse eyes causes ele
118 line-inducible (Tet-on) wild type and mutant
myocilin-
green fluorescence protein (GFP) expressing RGC
119 These results demonstrate that
myocilin has a de-adhesive activity and triggers signali
120 Wild-type (WT)
myocilin has been associated with steroid-induced glauco
121 Aggregation of wild-type
myocilin has been reported in other glaucoma subtypes, s
122 Elevated levels and aggregation of
myocilin hasten increased intraocular pressure and glauc
123 th steroid-induced glaucoma, and variants of
myocilin have been linked to early-onset inherited glauc
124 tial of MSCs and may identify a new role for
myocilin in bone formation and/or maintenance in vivo.
125 set out to develop a deeper understanding of
myocilin in its normal and diseased state.
126 inhibition are possible mechanisms by which
myocilin in overabundance may lead to TM cell or tissue
127 Recombinant
myocilin in porcine aqueous humor increased outflow resi
128 h induced expression of wild type and mutant
myocilin in RGC5 cell lines.
129 H) mice by promoting the secretion of mutant
myocilin in the aqueous humor and by decreasing intracel
130 Analysis of the
myocilin in the aqueous humor and TM revealed that PBA s
131 These data implicate a role for
myocilin in the development and/or maintenance of myelin
132 by decreasing intracellular accumulation of
myocilin in the ER, thus preventing TM cell death.
133 Overexpression of
myocilin in the eye angle tissues of transgenic mice sti
134 equivalent levels of mutated human or mouse
myocilin in the eyes of transgenic mice produce comparab
135 The expression of
myocilin in the iridocorneal angle tissues and aqueous h
136 mmunohistochemistry revealed the presence of
myocilin in the juxtacanalicular region of the trabecula
137 Expression of 15-fold higher levels of
myocilin in the muscles of transgenic mice led to the el
138 Accumulation of Y437H
myocilin in the TM induced endoplasmic reticulum stress
139 y be valuable in studies of proteins such as
myocilin in the TM.
140 transgenic mice expressed elevated levels of
myocilin in tissues of the iridocorneal angle.
141 intracellular accumulation of mutant and WT
myocilin in vitro, cell culture, and model organisms, th
142 of Grp94 promotes the degradation of mutant
myocilin in vitro, to date no Grp94-selective inhibitors
143 With some HTM cells,
myocilin increased to a greater extent when untreated ce
144 onstruct, but not with that of the wild-type
myocilin,
increased the apoptotic activity in cells.
145 ining was also noted in TM tissues of TAT-HA-
myocilin-
incubated or -perfused eyes.
146 TM cell cultures, after TAT-HA-
myocilin incubation, showed an enhanced myocilin stainin
147 Expression of mutated
myocilin induced its intracellular accumulation and prev
148 ocilin-expressing cells, as well as purified
myocilin,
induced the formation of stress fibers in prim
149 Myocilin-
induced elongation of oligodendrocyte processes
150 However, the pathogenic mechanisms of
myocilin-
induced glaucoma are still largely unknown.
151 ciferase reporter activity, fibronectin, and
myocilin induction in TM cells.
152 Myocilin induction was assessed after exposure of TM cel
153 Myocilin interacted with alpha1-syntrophin via its N-ter
154 When the Grp94-mutant
myocilin interaction is abrogated by inhibitors or siRNA
155 There,
myocilin interacts with gliomedin, neurofascin, and NrCA
156 nted secretion of both mutated and wild-type
myocilin into the aqueous humor.
157 Myocilin is a gene linked directly to juvenile- and adul
158 Myocilin is a gene linked to the most common form of gla
159 Here we demonstrate that
myocilin is a mediator of oligodendrocyte differentiatio
160 Myocilin is a protein found in the extracellular matrix
161 Myocilin is a protein found in the trabecular meshwork e
162 Myocilin is a secreted glycoprotein that belongs to a fa
163 Myocilin is a secreted glycoprotein that is expressed in
164 Although
myocilin is detected in several ocular and nonocular tis
165 In cells, when wild-type
myocilin is driven to misfold and aggregate, it becomes
166 is abrogated by inhibitors or siRNA, mutant
myocilin is efficiently degraded.
167 Myocilin is expressed and secreted by optic nerve astroc
168 Here we report that
myocilin is expressed in bone marrow-derived mesenchymal
169 We demonstrate that in sciatic nerve,
myocilin is expressed in Schwann cells with high concent
170 Myocilin is induced in response to several cellular stre
171 Mutant
myocilin is recognized by the endoplasmic reticulum (ER)
172 hen Grp94 is depleted, degradation of mutant
myocilin is shunted away from ERAD toward a more robust
173 Myocilin is thought to be a stress response protein, but
174 Myocilin is typically transported through the ER/Golgi n
175 The glaucoma-associated gene,
myocilin,
is expressed in ocular and non-ocular tissues
176 ER/Golgi network, but inherited mutations in
myocilin lead to its misfolding and aggregation within t
177 hronic expression of misfolded, non-secreted
myocilin leads to HTM cell death, trabecular meshwork dy
178 Expression of two mutant
myocilins led to different levels of endoplasmic reticul
179 glucocorticoids in TM cells, and an altered
myocilin level may be the culprit in conditions such as
180 tions of the anterior segment, and comparing
myocilin levels in the aqueous humor and trabecular mesh
181 dent antagonism to drug-induced increases in
myocilin levels.
182 es in understanding how genetic mutations in
myocilin likely lead to disease, but unlocking myocilin'
183 fibrils in aggregated forms of WT and mutant
myocilin localized to the C-terminal olfactomedin (OLF)
184 enes (fibronectin, collagen IV, collagen VI,
myocilin),
matricellular genes (connective tissue growth
185 One function of
myocilin may be to serve as a molecular chaperone.
186 cell growth and cell death, suggesting that
myocilin may have a role in the regulation of cell growt
187 Mutant
myocilins may confer different sensitivity to oxidative
188 r results suggest that expression of mutated
myocilins may have a sensitization effect, which can lea
189 undant functions in the mammalian eye, since
myocilin modulates Wnt signaling by interacting with com
190 e, the beta-propeller olfactomedin domain of
myocilin (
mOLF) exhibits a complex interrelationship amo
191 uced greater or similar amounts of SPARC and
myocilin mRNA after Lat-B treatment.
192 Myocilin mRNA and protein levels increased when HTM cell
193 SPARC and
myocilin mRNA expression were dramatically increased on
194 h surfaces, suggesting that the reduction of
myocilin mRNA when cells are plated onto flat tissue cul
195 8-month-old transgenic mice expressing Y437H
myocilin mutant.
196 genesis investigations of disease-associated
myocilin mutants.
197 r relatives of participants found to carry a
Myocilin mutation.
198 This is the first study to report
Myocilin mutations in an advanced POAG cohort.
199 The prevalence of
Myocilin mutations in glaucoma cases with severe visual
200 Prevalence and spectrum of
Myocilin mutations in individuals with advanced and nona
201 Identifying individuals who have
Myocilin mutations provides an opportunity to screen at-
202 The prevalence of
Myocilin mutations rose from 16% to 40% in selected adva
203 Exon 3
Myocilin mutations were identified in 45 advanced POAG p
204 No pathogenic
Myocilin mutations were identified in exons 1 and 2 in e
205 Twenty-six individuals with
Myocilin mutations were identified through cascade genet
206 ome a novel treatment for POAG patients with
myocilin mutations.
207 Mutations in
myocilin (
MYOC) are the most common genetic cause of pri
208 y open-angle glaucoma (POAG) patients with a
Myocilin (
MYOC) disease-causing variant who presented th
209 Myocilin (
MYOC) dominant gain-of-function mutations have
210 Sequence variations in the
myocilin (
MYOC) gene account for approximately 2% to 4%
211 on into a BAC carrying the full-length human
MYOCILIN (
MYOC) gene and long flanking regions.
212 Mutations in the
myocilin (
MYOC) gene are the most common genetic factors
213 Specific mutations in the
myocilin (
MYOC) gene cause primary open angle glaucoma (
214 ngle glaucoma by expression of mutated mouse
myocilin (
Myoc) in transgenic (Tg) mice.
215 Myocilin (
MYOC) is a protein with a broad expression pat
216 assettes were knocked into the 3'-UTR of the
Myocilin (
Myoc) locus, an abundantly expressed extracell
217 ies of wild-type and mutated mouse and human
myocilin (
Myoc) proteins as a prerequisite for developme
218 Herein, we investigated the role of
Myocilin (
Myoc), a skeletal muscle hypertrophy-promoting
219 collected for Western immunoblot analysis of
myocilin (
MYOC).
220 e glaucoma-associated olfactomedin domain of
myocilin (
myoc-OLF) is a recent addition to the growing
221 lved crystal structures of the OLF domain of
myocilin (
myoc-OLF), the best studied such domain to dat
222 Sciatic nerves of
myocilin null mice express reduced levels of several mye
223 lin sheath thickness of optic nerve axons in
Myocilin-
null mice compared with wild-type littermates,
224 Optic nerves of
Myocilin-
null mice contain reduced levels of several mye
225 f optic nerve oligodendrocytes is delayed in
Myocilin-
null mice.
226 amined the calcium binding properties of the
myocilin OLF domain (myoc-OLF).
227 rp94 recognizes on-pathway aggregates of the
myocilin olfactomedin domain (myoc-OLF), accelerates rat
228 ellular misfolding event involving a mutated
myocilin olfactomedin domain (OLF).
229 Similar to its family member
myocilin,
Olfm1 is stabilized by calcium.
230 -B dramatically downregulated both SPARC and
myocilin on 75 kPa hydrogels.
231 Stronger
myocilin or HA staining was also noted in TM tissues of
232 Transduction of
myocilin or myocilin-EGFP was evaluated by immunostainin
233 Assays further revealed that upon
myocilin overexpression, the activity of RhoA was dimini
234 EX and PRED significantly increased cellular
myocilin (
P < 0.0001), while GW870086X did neither.
235 l migration was consistent with demonstrated
myocilin phenotypes including the loss of actin stress f
236 Myocilin physically interacts with Lingo-1 and may be co
237 We suggest that intracellular
myocilin plays a role as a regulator of muscle hypertrop
238 re of quinary interactions between Grp94 and
myocilin points to a role for the far N-terminal sequenc
239 These results suggest that
myocilin promotes cell proliferation and resistance to a
240 Myocilin protected citrate synthase activity against the
241 C(50)s for PA were higher than DEX, for both
myocilin protein and mRNA.
242 Myocilin protein did not affect actin polymerization.
243 SPARC and
myocilin protein expression paralleled changes in mRNA e
244 hibitor reduced the levels of several mutant
myocilin proteins as well as wild-type myocilin when for
245 s performed to determine whether full-length
myocilin purified from a human trabecular meshwork cell
246 dy by the authors has shown that recombinant
myocilin purified from a prokaryotic expression system i
247 Myocilin purified from human trabecular meshwork cells i
248 These results indicate that aberrant
myocilin quaternary structure drives Grp94 recognition,
249 Expression of
myocilin rose during the course of human MSC differentia
250 ocilin likely lead to disease, but unlocking
myocilin'
s biological function is still an elusive goalp
251 Myocilin screening in phenotypically selected cases can
252 All three GCs increased fibronectin and
myocilin secretion in a concentration-dependent manner (
253 el SEGRA GW870086X increases fibronectin and
myocilin secretion similar to two traditional GCs, effec
254 In the context of full-length
myocilin,
secretion of stable single variants was indist
255 These data suggest that
myocilin should be considered as a target for improving
256 Myocilin signaling through ErbB2/3 receptors may contrib
257 Myocilin significantly reduced thermal aggregation of ci
258 The selected mRNAs (IL-6, IL-8,
myocilin,
SPARC [secreted protein, acidic and rich in cy
259 The mRNAs of
myocilin,
SPARC, and MMP-3, which do not have AREs, were
260 T-HA-myocilin incubation, showed an enhanced
myocilin staining compared with the control cultures.
261 isolated dorsal root ganglion cultures with
myocilin stimulates clustering of the nodal proteins neu
262 Myocilin stimulation of oligodendrocyte differentiation
263 facilitating folding and secretion of mutant
myocilin suggest a new type of treatment for this form o
264 nhibitor also facilitate clearance of mutant
myocilin,
suggesting that therapeutic approaches aimed a
265 Grp94 triages mutant
myocilin through ER-associated degradation, subverting a
266 lar expression and secretion of fibronectin,
myocilin,
tissue plasminogen activator (tPA), and/or mat
267 Genetic studies have linked
myocilin to open angle glaucoma, but the functions of th
268 The addition of mutant
myocilin to the short list of Grp94 clients strengthens
269 oprecipitation experiments and by binding of
myocilin to the surface of cells expressing cysteine-ric
270 This inhibitor rescued mutant
myocilin toxicity in primary human trabecular meshwork c
271 Human and bovine TM tissues after TAT-
myocilin transduction also exhibited a diminished actin
272 Myocilin transduction resulted in a loss of actin stress
273 Myocilin transfectants displayed a heightened sensitivit
274 nectin protein and mRNA were also reduced in
myocilin transfectants.
275 ibers and increased trypsin sensitivity from
myocilin transfection could be reverted by co-expression
276 ct on neurite outgrowth was also elicited by
myocilin transfection in RGC5 cells.
277 partially rescued by exogenous extracellular
myocilin treatment.
278 n 90 (Hsp90), specifically recognizes mutant
myocilin,
triaging it through ERAD.
279 ably transfected HEK293 cell line expressing
myocilin under an inducible promoter and compared gene e
280 essing wild-type or mutant (Y437H and I477N)
myocilins under an inducible promoter.
281 Is normal
myocilin unimportant in the human body?
282 n368Ter, the most common glaucoma-associated
myocilin variant.
283 Inherited, disease-causing
myocilin variants aggregate intracellularly instead of b
284 Both wild-type and certain
myocilin variants containing mutations in the olfactomed
285 Stress fiber-inducing activity of
myocilin was blocked by antibodies against myocilin, as
286 Expression of
myocilin was detected in MSCs derived from mouse, rat, a
287 ound up was reduced when wild type or mutant
myocilin was expressed.
288 Myocilin was isolated and purified from porcine trabecul
289 Mutant
myocilin was not secreted into the aqueous humor but acc
290 DMEM-FBS (442%), but only a 10% increase in
myocilin was observed beyond the normal induction in DME
291 tance in eyes incubated in DMEM, but only if
myocilin was preincubated with porcine aqueous humor (78
292 er the secreted, glaucoma-associated protein
myocilin was processed by this pathway.
293 Recombinant
myocilin was purified from the media using nickel ion af
294 All three exons of
myocilin were bidirectionally sequenced.
295 ver 20 years ago, alterations to the protein
myocilin were confirmed to be linked to a heritable form
296 Increased mRNA and protein levels of
myocilin were observed when cells were grown on 400-nm p
297 enic mice expressing 6-fold higher levels of
myocilin when compared with their wild-type littermates.
298 utant myocilin proteins as well as wild-type
myocilin when forced to misfold in cells.
299 Wild type
myocilin,
when transfected into cultured human TM cells,
300 Interaction of
myocilin with sFRP1, sFRP3, and several Frizzled recepto