Hög aktivitetsnivå / Nature skalar upp HoloMonitoruppmärksamheten

Högprofilerade vetenskapsorganet Nature publicerar i sin edition Scientific Reports en rapport från 11 forskare bördiga från amerikanska University of Iowa.

                                                         


 Forskningsrapporten som offentligjordes idag 6/9 är benämnd :

Imidazole Compounds for Protecting Choroidal Endothelial Cells from Complement Injury

Abstract
Age-related macular degeneration (AMD) is a common, blinding disease associated with increased complement system activity.
Eyes with AMD show elevated accumulation of the membrane attack complex (MAC) in the choriocapillaris and degeneration of macular choriocapillaris endothelial cells (ECs).
Thus, one could reasonably conclude that the endothelial cell death that occurs in AMD is due to injury by the MAC.
We therefore sought to identify strategies for protecting ECs against MAC lysis.
RF/6A endothelial cells were pre-incubated with a library of FDA-approved small molecules, followed by incubation with complement intact human serum quantification of cell death.
Two closely related molecules identified in the screen, econazole nitrate and miconazole nitrate, were followed in validation and mechanistic studies.
Both compounds reduced lysis of choroidal ECs treated with complement-intact serum, across a range of doses from 1 to 100 µM.
Cell rescue was confirmed in mouse primary choroidal ECs.
Both exosome release and cell surface roughness (assessed using a Holomonitor system) were reduced by drug pretreatment in RF/6A cells, whereas endosome formation increased with both drugs, consistent with imidazole-mediated alterations of cell surface dynamics.
The results in the current study provide further proof of principle that small molecules can protect choroidal ECs from MAC-induced cell death and suggest that FDA approved compounds may be beneficial in reducing vascular loss and progression of AMD.

Materials and Methods
(Här klipper jag in det som är PHI-relevant.)

Evaluation of cell surface characteristics following complement injury

Cells were plated on 6 well, TC-plates (Sarstedt, Numbrecht, Germany) at a confluency of approximately 15% and were incubated with 5% serum, either after incubation with vehicle alone (1% methanol) or after incubation with 50 µM econazole in vehicle for 4 hours.
After adding serum, cells were recorded using a Holomonitor M4 laser microscope (Phase Holographic Imaging, Lund, Sweden.) Images were recorded every 10 minutes for 24 hours.
The average cellular roughness (an estimate of the difference in cell surface topography between the theoretical rounded cell and the actual pixel values) was quantified in all treatments using Hstudio M4 software (version 2.7.1).

Drug pretreatment with econazole alters complement induced cell surface roughness

Cell surface features were quantified using a holomonitor M4 laser microscope system.
Cellular “roughness” is a measurement of cell surface topography and is estimated as the difference between the mathematically rounded cell surface and the actual recorded position of each pixel (http://www.phiab.se/reports/manuals/M4-SetupAndOperationManual.pdf).
Cells treated with complement containing serum showed increased roughness compared to untreated controls, whereas cells exposed to econazole for 4 hr prior to serum challenge showed significantly decreased roughness compared to serum treatment alone over 24 hours of observation, particularly after the first 12 hours (Fig. 4A,B).

Min kommentar
Forskarna har studerat ett riktigt jobbigt problem för den äldre populationen.
Nämligen synnedsättning som i värsta fall leder till blindhet.
AMD = Åldersrelaterad makuladegenering, den främsta anledningen till blindhet hos seniorbefolkningen.
I dagsläget har läkarkåren inget generellt och allmänt godkänt svar på hur förebygga eller bota vid uppkomst. Forskare från Australien har gett sig på att hitta ett effektivt botemedel som i bästa fall lindrar och/eller stannar upp förloppet. Med laserteknik har forskare från University of Melbourne kommit en bit på vägen.
Men det forskarna här nu i sin rapport visar är att forskning på celler i ögats minsta beståndsdelar kan förklara sjukdomens uppkomst och med den nya kunskapen gå vidare för att hitta botemedel.
Från rapporten: Eyes with AMD show elevated accumulation of the membrane attack complex (MAC) in the choriocapillaris and degeneration of macular choriocapillaris endothelial cells (ECs). 
Thus, one could reasonably conclude that the endothelial cell death that occurs in AMD is due to injury by the MAC.
The results in the current study provide further proof of principle that small molecules can protect choroidal ECs from MAC-induced cell death and suggest that FDA approved compounds may be beneficial in reducing vascular loss and progression of AMD. 
Läser man vidare i rapporten framkommer att forskarna testat idag FDA-godkända molekylsammansättningar (ekonazolnitrat och mikonazolnitrat) som motmedel för att stanna upp den celldöd och kärlförlust som leder till AMD. Dessa rön kan vara svaret läkarkåren efterfrågat.
Med hjälp av PHI,s HoloMonitor har forskarna kommit till dessa (för oss alla som seniorer ska bli) glädjande resultat.
Ni noterar väl även att forskarna bifogade en länk till HoloMonitorn i sin rapport?
Det är sanslöst bra PR för PHI.
Ska vi gissa att forskare världen över som läser denna rapport klickar in sig på Bolagets hemsida och då får reda på HoloMonitorns existens? Och fortsätter vi gissa - hur många av dessa äskar medel för att investera i eget HoloMonitorinstrument?
VD borde skicka den allra största chokladasken till rapportens upphovsmän/kvinnor. 😎

AMD