Nuestros investigadores

Elena Alonso Iglesias


Publicaciones científicas más recientes (desde 2010)

Autores: Fernández Robredo, Patricia; Sáenz de Viteri Vázquez, Manuel; Recalde Maestre, Sergio; et al.
ISSN 0146-0404  Vol. 57  Nº 12  2016  págs. 3363
Purpose : To evaluate intracellular accumulation and the effect of bevacizumab, ranibizumab and aflibercept on cellular migration and permeability in a human retinal pigmented epithelium (RPE) cell line. Methods : Experiments were performed on ARPE-19 cells and anti-VEGF drugs were diluted to a concentration equivalent to their clinical doses. Anti-VEGFs were labeled with Alexa 488 fluorochrome to detect intracellular accumulation by flow cytometry at 1 hour, 1 day and five days. Further, transepithelial electrical resistance (TEER) was measured in transwells at 2, 4, 6, 12 and 24 hours to assess the effect of anti-VEGFs on RPE permeability. Moreover, TEER was also measured at the same time points in the presence of different doses of H2O2 to replicate the oxidative environment observed in Age-related Macular Degeneration (AMD). Wound healing was assessed to determine the effect of the drugs on cellular migration during 72 hours to measured cell covered area by ImageJ software. Results : The three studied drugs were observed to accumulate inside the cells and they were still detectable five days after being added (p<0.001). A dose-dependent increased in cell permeability was observed in cells treated with H2O2 (p<0.05) that was reverted from the time point of 12 hours and became non-significant. Anti-VEGF drugs did not affect the permeability along time and they were able to reduce the effect of H2O2. Cells treated with anti-VEGF drugs at the beginning of the experiment showed a significant decrease in the damage produced by H2O2 at 4, 6 and 12 hours (p<0.05) with no significant difference between the treatments. On the contrary, when anti-VEGF treatment was used 6 hours after the beginning of the experiment, none of the 3 drugs decreased the deleterious effect of H2O2 in TEER. Anti-VEGF drugs did not affect cellular migration. Conclusions : Intracellular accumulation of bevacizumab, ranibizumab and aflibercept does not seem to be toxic or affect cell permeability and migration. Moreover, our study suggests that anti-VEGFs have a positive effect on the barrier function of the RPE.
Autores: Ortega Cubero, Sara; Lorenzo-Betancor, O., ; Lorenzo Ramos, María Elena; et al.
ISSN 0197-4580  Vol. 34  Nº 10  2013  págs. 2441.e9 - 2441.e11
FUS/TLS (denoting fused in sarcoma/translocated in liposarcoma [MIM 137070]) codifies an RNA binding protein. Mutations in this gene cause amyotrophic lateral sclerosis (ALS; MIM 608030). Essential tremor (ET [MIM 190300]) is the most frequent movement disorder. Despite its strong familiar aggregation, recently a whole exome sequencing study has identified FUS mutations as a cause of familial ET. To determine whether mutations in FUS are also common in other populations, we sequenced FUS gene in 178 unrelated Spanish subjects with ET. We detected only an intronic single-pair nucleotide deletion (c.1293-37delC), which was predicted to affect mRNA splicing. However, leukocyte mRNA analysis showed no changes in FUS expression. In conclusion, coding or splicing FUS mutations are not a frequent cause of ET in the Spanish population.
Autores: Cervantes Ibáñez, Sebastián; Vidal Taboada, José Manuel; Lamet Gil, María Isabel; et al.
Revista: Neurobiology of Aging
ISSN 0197-4580  Vol. 32  Nº 11  2011  págs.  2107. e7- 17
We report the fine mapping/sequencing results of promoter and regulatory regions of APOE cluster genes (APOE, APOC1, APOC4, APOC2, and TOMM40) in Alzheimer's disease (AD) risk as well as in the progression from mild cognitive impairment (MCI) to AD. Long-range sequencing in 29 MCI subjects who progressed to dementia revealed 7 novel variants. Two potentially relevant novel variants and 34 single nucleotide polymorphisms (SNPs) were genotyped in a large sample of AD, MCI, and control subjects (n = 1453). Globally, very little association signal was observed in our sample in the absence of APOE ¿4. Rs5158 (APOC4 intron 1) and rs10413089 (3' to APOC2) showed a trend toward an increase in AD risk independently from APOE ¿4 associated risk though it did not survive multiple test correction (uncorrected p = 0.0099 and 0.01, respectively). Interestingly, rs10413089 showed a similar effect in an independent series. The analysis of the discovery sample showed an association of TOMM40 single nucleotide polymorphisms with progression from MCI stage to AD (rs59007384 and rs11556510), as well as with a shorter time to progression from MCI status to AD (rs10119), though these results could not be replicated in independent series. Further studies are needed to investigate the role of APOE cluster variants in AD risk.