Here is again a new eye paper by Dr. Nquyen and Prof Finkelstein demonstrating alpha-synuclein interaction in the retina, which provides a new screening tool for fast-tracking potential PD drugs. I would be almost sure that they have tested ATH434 in this model at least in the primate study but maybe many other molecules ATH has patented. A very speedy method of testing potential new drugs.Levodopa Rescues Retinal Function in the Transgenic A53T Alpha-Synuclein Model of Parkinson's Disease
AffiliationsDOI: 10.3390/biomedicines12010130
- PMID: 38255235
Abstract
Background: Loss of substantia nigra dopaminergic cells and alpha-synuclein (α-syn)-rich intraneuronal deposits within the central nervous system are key hallmarks of Parkinson's disease (PD). Levodopa (L-DOPA) is the current gold-standard treatment for PD. This study aimed to evaluate in vivo retinal changes in a transgenic PD model of α-syn overexpression and the effect of acute levodopa (L-DOPA) treatment.
Methods: Anaesthetised 6-month-old mice expressing human A53T alpha-synuclein (HOM) and wildtype (WT) control littermates were intraperitoneally given 20 mg/kg L-DOPA (50 mg levodopa, 2.5 mg benserazide) or vehicle saline (n = 11-18 per group). In vivo retinal function (dark-adapted full-field ERG) and structure (optical coherence tomography, OCT) were recorded before and after drug treatment for 30 min. Ex vivo immunohistochemistry (IHC) on flat-mounted retina was conducted to assess tyrosine hydroxylase (TH) positive cell counts (n = 7-8 per group).
Results: We found that photoreceptor (a-wave) and bipolar cell (b-wave) ERG responses (p < 0.01) in A53T HOM mice treated with L-DOPA grew in amplitude more (47 ± 9%) than WT mice (16 ± 9%) treated with L-DOPA, which was similar to the vehicle group (A53T HOM 25 ± 9%; WT 19 ± 7%). While outer retinal thinning (outer nuclear layer, ONL, and outer plexiform layer, OPL) was confirmed in A53T HOM mice (p < 0.01), L-DOPA did not have an ameliorative effect on retinal layer thickness. These findings were observed in the absence of changes to the number of TH-positive amacrine cells across experiment groups. Acute L-DOPA treatment transiently improves visual dysfunction caused by abnormal alpha-synuclein accumulation.
Conclusions: These findings deepen our understanding of dopamine and alpha-synuclein interactions in the retina and provide a high-throughput preclinical framework, primed for translation, through which novel therapeutic compounds can be objectively screened and assessed for fast-tracking PD drug discovery.
- Forums
- ASX - By Stock
- ATH
- Levodopa rescues retinal function in PD model by Finkelstein et al
Levodopa rescues retinal function in PD model by Finkelstein et al
- There are more pages in this discussion • 3 more messages in this thread...
You’re viewing a single post only. To view the entire thread just sign in or Join Now (FREE)
Featured News
Add ATH (ASX) to my watchlist
(20min delay)
|
|||||
Last
0.5¢ |
Change
-0.001(10.0%) |
Mkt cap ! $26.22M |
Open | High | Low | Value | Volume |
0.5¢ | 0.5¢ | 0.5¢ | $939 | 208.6K |
Buyers (Bids)
No. | Vol. | Price($) |
---|---|---|
64 | 90139720 | 0.4¢ |
Sellers (Offers)
Price($) | Vol. | No. |
---|---|---|
0.5¢ | 29445801 | 20 |
View Market Depth
No. | Vol. | Price($) |
---|---|---|
63 | 90014720 | 0.004 |
49 | 52645564 | 0.003 |
17 | 39293014 | 0.002 |
14 | 94870101 | 0.001 |
0 | 0 | 0.000 |
Price($) | Vol. | No. |
---|---|---|
0.005 | 29445801 | 20 |
0.006 | 34944496 | 19 |
0.007 | 17531813 | 17 |
0.008 | 14585875 | 16 |
0.009 | 6275000 | 7 |
Last trade - 11.06am 14/06/2024 (20 minute delay) ? |
Featured News
ATH (ASX) Chart |