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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How new medical codes can boost use of digital therapeutic tools

The increasing and continuing doctor interest in making use of digital health equipment is being supported by a steadily establishing regulatory framework and an infrastructure that produces a pathway to payment though defining how equipment and software package can aid treat, take care of and stop illness.

An AMA doctor study (PDF), carried out each individual 3 a long time, finds adoption of digital wellness equipment has developed appreciably between all doctors regardless of gender, specialty or age, with improved scientific outcomes and operate effectiveness discovered as the crucial motorists of adoption.

The digital overall health applications that garner the most enthusiasm amongst medical professionals are televisits (57{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}) followed by distant-monitoring equipment (53{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f}).

The premier advancement in adoption was among the digital health equipment that help in distant treatment with the proportion of physicians working with remote-checking devices reaching 30{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} in 2022, compared with only 12{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} in 2016.

The 2016 survey also surfaced the four inquiries that doctors want to know about new rising electronic wellbeing methods:

When it comes to validating the efficiency and safety of these remote applications, the Food and Drug Administration (Food and drug administration) regulates them in its Software program as a Healthcare Device class.

In conditions of making certain proper payment, the Present-day Procedural Terminology (CPT®) code set classifies them as both instruments for distant physiologic monitoring (RPM) or remote therapeutic monitoring (RTM).

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What physicians will need to know about E/M code variations coming Jan. 1

RPM tools evaluate data in purchase to appropriately take care of disease. RTM applications expand entry to remote checking and checking of facts linked to symptoms, signs and symptoms and capabilities of a therapeutic reaction.

“The CPT Editorial Panel has put in a lot of time and work more than the very last couple years creating confident that the CPT code established is robust in this spot,” mentioned Zachary Hochstetler, the AMA’s director of CPTeditorial and regulatory affairs, for the duration of “Digital Therapeutics: In Apply,” a totally free on-desire AMA webinar. (Registration essential.)

This year’s Outpatient CDI Workshop and CPT and RBRVS 2023 Once-a-year Symposium are being held virtually Nov. 15–18. Remain up to day on important CPT code and relative worth device (RVU) modifications for 2023. Register now.

Electronic therapeutics (DTx) “deliver therapeutic interventions specifically to clients using evidence-centered, clinically evaluated software program to take care of, deal with and stop a broad spectrum of behavioral, mental, and physical disorders and problems,” according to the Electronic Therapeutics Alliance, a trade affiliation of field stakeholders engaged in the evidence-pushed advancement of DTx.

The alliance lists examples of DTx that assist in the remedy of sort 2 diabetic issues, generalized stress and anxiety ailment, melancholy, migraine, sleeplessness and more.

“Anything that is purely medical selection support or purely a monitoring instrument or a like an electronic wellness report in fact is not a digital therapeutic mainly because it really is not actually providing a therapy to a client,” Megan Coder, PharmD, the main policy officer and founder of the Electronic Therapeutics Alliance, said during the webinar.

An essential distinction Coder pointed out is that, although the RTM application is hosted on a common gadget or even on a product particularly made to host the DTx instrument, it is the software—and not the device—that is “directly treating, managing or protecting against a ailment or disorder and is made use of in the context of clinical care.”

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How the 2023 CPT code set will enable lower administrative burdens

RPM CPT codes ended up produced in 2019 and protect setup and educating individuals on use of the devices, unit supply and the administration of affected person therapy, Hochstetler mentioned.

The RPM codes are intended to be utilized in the monitoring of a patient’s physiologic parameters this sort of as body weight, blood force, pulse oximetry or respiratory stream amount.

“The key way in which these are used is to assess info remotely in order to properly take care of disease—and so that’s just at the best degree what they are intended to do,” Hochstetler discussed.

“What the CPT code lacked right before 2019 was a holistic code loved ones for the price tag of the unit, the price of the client coaching that was going on or just about anything else that was outside of the physician’s operate,” he added.

The RTM CPT codes were produced this year and are also made use of for machine source, product setup and affected person schooling in their use, as nicely as client adherence and response to treatment.

These new distant therapeutic monitoring codes concentrate on musculoskeletal program standing, respiratory procedure status, remedy adherence and remedy response, and stand for the critique and checking of knowledge connected to a therapeutic reaction,

Discover extra with AMA Ed Hub™ CPT Schooling. The CPT Network is also available for authoritative CPT coding steering.