According to a recent study, people who spend more than 2 hours a day on digital devices are 2.5 times […]
Purpose : Smith-Lemli-Opitz syndrome (SLOS), caused by mutations in the gene for 7-dehydrocholesterol reductase, catalyzes the last step in cholesterol (CHOL) synthesis. Oxysterols derived from the CHOL precursor 7-dehydroCHOL accumulate in tissues of affected individuals, and are toxic to photoreceptors in our non-genetic rat model of SLOS. We previously reported results from a gene array performed on 661W cells (a mouse cone-derived cell line) treated with a SLOS-specific oxysterol (EPCD), as well as with 7-ketoCHOL, showing that loss of viability was associated with differentially expressed genes (DEG) involving CHOL synthesis, ER/oxidative stress, DNA damage, and autophagy pathways. Here, we further mined the array data for enrichment related to CHOL efflux, iron and heme metabolism, synapses, circadian clock, and autism spectrum disorder (ASD), a neurological defect found in SLOS patients.
Methods : As previously described, 661W cultures were incubated (n=3) with either oxysterols, CHOL, or vehicle control (VC). RNA samples were harvested prior to global loss of viability. After conversion of raw data, mean fold changes (FC) vs. VC, and adjusted P-values (aP) were computed; thresholds for DEG were FC ≥ 1.5 and aP ≤ 0.001. Enrichment analysis utilized LRpath.
Results : ABCA1 was significantly upregulated by treatment with EPCD and 7-ketoCHOL, but not CHOL. Along with elevated expression of HMOX1, oxysterols induced DEG for heme synthesis and its regulation, bilirubin and iron cycling, and ferroptosis. The EPCD DEG set showed enrichment of genes related to synaptic structure and function (P<10E-6; almost all down-regulated), with 40/120 among the top 2500 ASD candidates from a gene interaction network (asd.princeton.edu). Annotations for ASD-associated processes from EPCD-treated samples also indicated dysregulation (P<0.05) of: cell junctions, cell-matrix adhesion, methyltransferase activity, and signaling via wnt, kinases, and growth factors. Upstream and downstream effectors for “ASD genes” RELN, FMR1, and MECP2 were also affected. Both oxysterols (and CHOL to a lesser extent) dysregulated numerous DEG for clock function, including CLOCK, RORA, and NR1D2.
Conclusions : Using disease-specific metabolites exogenously applied to an otherwise unaffected photoreceptor cell line, we show that this in vitro model of SLOS may be exploited to further elucidate the molecular basis for neurological disease.
Vision therapy is well worth the response, time and effort. Our Son had a hard time focusing and writing neatly. After vision therapy Seth could complete a task in half the time if previously took. His abilities to focus improved greatly and so did his handwriting.
Also, he was better at listening. As a parent, we wanted learning to be fun for our Son, and vision therapy made this possible.
Vision Therapy is well worth the expense, time and effort. Our son had a hard time focusing handwriting neatly. After vision therapy Seth could complete a task in half the time it previously took his abilities to focus and improved greatly and so did his handwriting.
Also, he was better at listening. As a parent you wanted learning to be fun for our son and vision therapy made this possible.
Vision Therapy has given or son the tools he needs to be able to scan and read the written word more effectively and efficiently.
He love working with John and these working sessions give him the motivation to gladly work on his homework assignments.
It amazed us to see the difference in the tracking of his eyes and along a line of it's from the beginning to the end of the treatment.
Dr. McBryar , Kristen and John are all marvelous and we would recommend them to anyone I only wish that we would have found them sooner!
Prior to coming to the institute for vision development my son complained of daily headaches. Therapy has eliminated his headaches completely. I love knowing my son is able to learn pain-free for the rest of his life because of the work that has been done over just a few weeks in this office. He he absolutely loved coming that didn't even feel like going to a doctor or therapy. We are grateful for the relief he was able to find by coming here.
Seems much less frustrated with life
Reads non-stop and fast
Spelling abilities have been hugely improved
Seems much more confident
When we first came to the practice, my son did not have huge issues, but lots of small ones- trouble with reading, sports (hitting the baseball consistently), coordination, etc- that were not easily detectable,but when put together presented issues. The staff here were all very professional and loving towards him. While I was concerned in the reading, my son was concerned with the athletic side. Seeing improvement night off the bat gave him confidence that i have nor seen in him and made him want to not only Come to therapy, but also made him want to work hard. He has surpassed his grade level and above in reading and hit his first home run this year! Thank you!!!
Many people believe that good eyesight is simply the ability to read the "20/20" line on an eye chart, but […]
Corneal abrasions, or scratched corneas, are a common occurrence and make up a significant portion of eye injury cases. In […]