Tag: target

Researchers discover therapeutic target to aid in glaucoma treatment

Researchers discover therapeutic target to aid in glaucoma treatment
hRGCs maintain mitochondrial mass by simultaneous degradation and biogenesis of mitochondria under damage. a, b Representative confocal immunofluorescence images of H7-hRGCs against mitochondrial Tom20, tdTomato, and DAPI after indicated 10 μM CCCP treatment timepoints. Scale bars are 5 μm. c, d Quantification of Tom20 intensity per cell area from sum projections of confocal z-stacks, normalized to corresponding DMSO. n = 14–42 cells per condition. e, f Mitochondrial DNA copy number analyzed by qPCR for mitochondrial ND1 gene relative to nuclear RNase P. Results shown as ΔΔCt fold changes relative to DMSO control for different times points of 10 μM CCCP treatment. n = 3, 3 technical repeats averaged for each biological repeat. g Schematic of MTDR flow experiments for tracking degrading versus newly synthesized mitochondria. h Mitochondrial mass in single cells at different CCCP (10 μM) treatment time points for degradation or m different timepoints post CCCP (10 μM) wash for biogenesis were measured by flow cytometer, and the average fluorescence intensity normalized to DMSO was plotted. n = 3. i, k Representative western blot images of LC3B and actin from i hRGCWT and k hRGCE50K treated with CCCP (10 μM) for the indicated timepoints. j, l Quantification of the ratio of LC3B-II to corresponding LC3B-I for each condition. n = 3. ٭p-value < 0.05, ٭٭p-value < 0.01, ٭٭٭p-value < 0.001, ٭٭٭٭p-value < 0.0001. Unpaired student’s t-test between independent datasets. Error bars are SEM. Credit: Communications Biology (2023). DOI: 10.1038/s42003-023-04576-w

Indiana University School of Medicine researchers have identified a new therapeutic target that could lead to more effective treatment of glaucoma.

Glaucoma is a neurodegenerative disease that causes vision loss and blindness due to a damaged optic nerve. More than 200,000 people are affected by glaucoma in the United States each year. Unfortunately, there is currently no treatment. In a newly published paper in Communications Biology, researchers found neurons use mitochondria for a steady source of energy, and restoring mitochondrial homeostasis in the diseased neurons can protect the optic nerve cells from being damaged.

“Age-related neurodegenerative disease, which includes glaucoma, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), is the biggest global health problem,” said Arupratan Das, Ph.D., assistant professor of ophthalmology and principal investigator of the study.

“The fundamental mechanisms that we discovered can be used to protect neurons in glaucoma and be tested for the other diseases. We have identified a critical step of complex mitochondrial homeostasis process, which rejuvenates the dying neuron, similar to giving a lifeline to a dying person.”

The research team, led by Michelle Surma and Kavitha Anbarasu from the Department of Ophthalmology, used induced pluripotent stem cells (iPSCs) from patients with and without glaucoma as well as clustered regularly interspaced short palindromic repeats (CRISPR) engineered human embryonic stem cells with glaucoma mutation.

Using stem cell differentiated retinal ganglion cells (hRGCs) of the optic nerve, electron microscopy and metabolic analysis, researchers identified glaucomatous retinal ganglion cells suffer mitochondrial deficiency with more metabolic burden on each mitochondrion. This leads to mitochondrial damage and degeneration. Mitochondria are the tube like structures in cells which produce adenosine triphosphate, cell’s energy source.

However, the process could be reversed by enhancing mitochondrial biogenesis by a pharmacological agent. The team showed retinal ganglion cells are highly efficient in degrading bad mitochondria, but at the same time producing more to maintain homeostasis.

“Finding that retinal ganglion cells with glaucoma produce more adenosine triphosphate even with less mitochondria was astonishing,” Das said. “However, when triggered to produce more mitochondria, the adenosine triphosphate production load was distributed among more mitochondrion which restored the organelle physiology. It is similar to a situation where a heavy stone is carried by fewer people versus a greater number of people—each person will have less pain and injury, just like each mitochondrion will have less difficulty and damage.”

In the future, Das would like to test if these mechanisms protect the optic nerve in animal models under injury before testing in humans to hopefully lead to new clinical interventions.

More information:
Michelle Surma et al, Enhanced mitochondrial biogenesis promotes neuroprotection in human pluripotent stem cell derived retinal ganglion cells, Communications Biology (2023). DOI: 10.1038/s42003-023-04576-w

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Indiana University School of Medicine


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CU Winter Giving Efforts Target Students, the Homeless & Medical Research

CU Winter Giving Efforts Target Students, the Homeless & Medical Research AmeriCU

Staff users from the $2.6 billion, Rome, N.Y.-centered AmeriCU’s Liverpool Economical Middle in Liverpool, N.Y., gear up for the credit score union’s thirty day period-extended American Coronary heart Affiliation marketing campaign. For the duration of the thirty day period of February, members can take part in the AHA’s Have a Coronary heart campaign by stopping by any AmeriCU branch to obtain a red coronary heart to raise awareness for heart wellness in their communities. The money lifted will go towards lifetime-preserving analysis that assures anyone has an chance to get pleasure from a healthful existence cost-free from heart ailment and stroke.

First Financial FCU Initially Fiscal FCU

Andrea Rapp (suitable), marriage marketing manager for the $1.2 billion, Sparks, Md.-centered Initial Economic Federal Credit history Union, presents a check to Carroll Group Higher education Foundation Government Director Steven L. Wantz. FFFCU just lately pledged $100,000 about a five-calendar year time period to the Basis, with options to donate $20,000 each and every calendar year through the 2027-28 school yr. Proceeds will gain the Foundation’s athletic program, new commence software and scholar emergency aid fund. In addition, the credit rating union donated $10,000 to the non-revenue Carroll County Foodstuff Sunday and $5,000 to its lover of 32 several years, Carroll County Community Educational facilities.

Neighborhood CU Community CU

Sharon Garfield, a 10-12 months member of the $1 billion, Dallas, Texas-centered Community Credit score Union, receives a shock $49,999 reward for her excellent financial savings habits just after becoming preferred as the credit union’s 2023 Prize Cost savings Account grand prize winner. All over the yr, Prize Personal savings Account holders acquire a single drawing entry for every single $25 regular monthly typical stability in their account. They are then eligible for weekly drawings, culminating with the once-a-year grand prize, which is drawn each individual Jan. 1 centered on the typical month-to-month harmony in their account at the near of the organization day on Dec. 31.

RTN FCU RTN FCU

Michael Menas, branch manager for the $1 billion, Waltham, Mass.-dependent RTN Federal Credit Union, displays handmade donated blankets. RTN just lately donated dozens of handmade blankets, as nicely as $250 toward the purchase of blankets, clothes and pajamas, to the Massachusetts Coalition for the Homeless’ A Bed for Each Little one System. The energy was part of the Present of Warmth Blanket and Clothes Push that is coordinated just about every winter season by the Cooperative Credit score Union Association. The blankets for infants and kids had been knitted by volunteers from Blankets 4 Youngsters, a knitting, quilting and sewing team from the Amesbury Senior Community Heart in Amesbury, Mass., precisely for the yearly generate.

SAFE CU Safe and sound CU

Two residents of Sacramento Cottage Housing Inc. in Sacramento, Calif., display off their artwork. The $4.5 billion, Folsom, Calif.-dependent Safe and sound Credit Union not too long ago awarded a $5,000 grant to Cottage Housing to fund new instructional programs for its formerly homeless consumers so they can discover crucial lifetime and economic expertise. The grant was awarded as a result of the credit union’s Community Sustainability Grant Software, and in December, Protected invited the neighborhood to choose two grant recipients presenting education courses that address inequities. Voters selected Cottage Housing and the Construction Market Education Foundation to every obtain $5,000 grants. (Photo: Sacramento Cottage Housing Inc.)

SeaComm FCU SeaComm FCU

Previous November, the $775 million, Massena, N.Y.-centered SeaComm Federal Credit score Union pledged $50,000 to support associates in have to have with dwelling heating expenditures. Associates utilized for the grant on the net, in branches and via mail through Jan. 6, and after just about 1,000 apps were submitted, SeaComm’s Winter season Gas Grant Committee cautiously picked 100 associates to receive gas grants worthy of $500 every single. At the time picked, the recipients were being notified, and the money were being dispersed to nearby gasoline providers for credit to their account. Pictured from left to appropriate are Dealer Romance Supervisor Danielle Uppstrom, House loan Supervisor Tara Cusworth, President/CEO Scott A. Wilson and Personal loan Functions Agent Chandler LaPlante, all with SeaComm.

You should send out your Neighborhood news objects to Natasha Chilingerian at [email protected]

Transgender youth health care bans have a new target: adults

Lawmakers in at minimum 3 states this 12 months have submitted legislation meant to restrict accessibility to gender-affirming wellness treatment for men and women as outdated as 26, an escalation of a struggle waged nationwide final calendar year more than regardless of whether minors ought to be equipped to entry particular prescription remedies and techniques.

Expenses filed this year in Oklahoma, South Carolina and Virginia aim to bar state well being care companies from recommending or administering solutions like puberty blockers, hormones and gender-affirming surgeries to clients youthful than 21, signaling an aggravation in the fight about transgender overall health treatment.

Another Oklahoma bill filed this thirty day period would prohibit older people up to 25 from acquiring gender-affirming care in one of the most serious and restrictive bans launched to date. The state’s proposed “Millstone Act,” which gets its name from a Bible verse about punishing grownups who damage youngsters, would also block Oklahoma’s Medicaid program from giving coverage for “gender transition procedures” to folks youthful than 26.

“I don’t think it was at any time about youngsters,” Erin Reed, an unbiased legislative researcher, advised The Hill this week, referring to point out and federal attempts to ban gender-affirming treatment more than the previous two decades.

GOP legislators’ arguments against transgender well being treatment have in the earlier centered all-around a have to have to defend young children from alleged predatory health professionals and “woke” gender ideology. Charges filed across the place final yr utilized inflammatory and deceptive rhetoric to disparage gender-affirming treatment for youth with titles like the “Save Adolescents from Experimentation Act” and the “Protect Children’s Innocence Act.”

“These adult bans display that which is not what it was about,” Reed mentioned. “It’s about banning treatment totally. It’s about forcing transgender persons back in the closet.”

Point out legislators have not moved absent from youth overall health treatment bans fully, and dozens of costs searching for to ban gender-affirming treatment completely for minors have by now been introduced in much more than 10 states this calendar year.

Reed extra that she’s skeptical whether or not legislators sponsoring adult well being care bans this year hope these steps to move as penned. It is possible, she stated, that lawmakers are concentrating on older folks to make youth health and fitness care bans show up less serious and additional palatable.

“This is, in component, a way that they are trying to make it less difficult to move gender-affirming care bans for smaller teams in the inhabitants,” she mentioned.

Efforts to prohibit transgender adults’ accessibility to wellbeing care lean intensely on claims from so-named “gender-critical” organizations that youthful individuals ought to not be recognized as grownups right before they transform 25, when the human mind is thought to reach entire maturity.

Point out GOP lawmakers in Missouri final year weighed extending a proposed youth health and fitness care ban to grownups below 25, arguing that men and women even into their early 20s are not able to absolutely consent to gender-affirming interventions.

That and similar claims have been disputed by professional medical professionals and doctors with knowledge treating transgender youth, and a number of inquiries have observed that affirming a boy or girl or adolescent’s gender id can boost their mental wellness results into adulthood.

Passing regulations to hold off well being care considered medically essential by most main health-related associations is also dangerous, in accordance to Dr. Meredithe McNamara, an assistant professor of pediatrics at Yale College, and runs the danger of worsening costs of panic, despair and suicidality between transgender youth and youthful grown ups having difficulties with gender dysphoria.

Just about 20 {bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of transgender and nonbinary 13- to 24-year-olds surveyed very last 12 months by The Trevor Project, a main LGBTQ youth suicide avoidance business, reported they had tried suicide in the previous yr. Much less than a 3rd said their gender identity was affirmed at home.

For McNamara, who treats transgender youth aged 11-25, the principal problem with grownup well being care bans lies with folks below 21 — or 26, in Oklahoma’s scenario — who are currently getting gender-affirming health-related treatment.

“There are folks now on therapy, dwelling as their reliable selves and suffering from aid from gender dysphoria who facial area forcible detransition,” she stated.

None of the proposed measures include things like language or provisions that explicitly tackle transgender youth and youthful older people by now obtaining medicines like hormones or puberty blockers.

Attempts to restrict gender-affirming health treatment for grownups also possibility backfiring by restricting the freedoms of people today who can lawfully vote, drink a beer and go to war. They also discriminate centered on sexual intercourse and transgender status, according to Chase Strangio, deputy director for transgender justice at the American Civil Liberties Union LGBTQ & HIV Venture, generating them unconstitutional.

“It’s not about defending any person,” Strangio claimed of recent legislative attempts to limit gender-affirming care. “It’s about an opposition to trans identification.”