Options
Moya-Albor, Ernesto
Lack of Delta-Sarcoglycan (Sgcd) Results in Retinal Degeneration
Nuclear density analysis in microscopic images for the characterization of retinal geographic atrophy
2019
,
Pérez Ortiz, Andric Christopher
,
Peralta-Ildefonso, Martha Janneth
,
Lira, Esmeralda
,
Ramírez-Sánchez, Israel
,
Brieva, Jorge
,
Moya-Albor, Ernesto
,
Clapp, Carmen
,
Luna-Angulo, Alexandra
,
Rendon, Álvaro
,
Adan-Castro, Elva
,
Ramírez-Hernández, Gabriela
,
Díaz-Lezama, Nundehui
,
Coral-Vázquez, Ramón
,
Estrada Mena, Francisco Javier
Age-related macular degeneration (AMD) is the leading cause of central vision loss and severe blindness among the elderly population. Recently, we reported on the association of the SGCD gene (encoding for δ-sarcoglycan) polymorphisms with AMD. However, the functional consequence of Sgcd alterations in retinal degeneration is not known. Herein, we characterized changes in the retina of the Sgcd knocked-out mouse (KO, Sgcd−/−). At baseline, we analyzed the retina structure of three-month-old wild-type (WT, Sgcd+/+) and Sgcd−/− mice by hematoxylin and eosin (H&E) staining, assessed the Sgcd-protein complex (α-, β-, γ-, and ε-sarcoglycan, and sarcospan) by immunofluorescence (IF) and Western blot (WB), and performed electroretinography. Compared to the WT, Sgcd−/− mice are five times more likely to have retinal ruptures. Additionally, all the retinal layers are significantly thinner, more so in the inner plexiform layer (IPL). In addition, the number of nuclei in the KO versus the WT is ever so slightly increased. WT mice express Sgcd-protein partners in specific retinal layers, and as expected, KO mice have decreased or no protein expression, with a significant increase in the α subunit. At three months of age, there were no significant differences in the scotopic electroretinographic responses, regarding both a- and b-waves. According to our data, Sgcd−/− has a phenotype that is compatible with retinal degeneration. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
2020
,
Peralta Ildefonso, Martha Janneth
,
Moya-Albor, Ernesto
,
Brieva, Jorge
,
Lira, Esmeralda
,
Pérez Ortiz, Andric Christopher
,
Coral-Vázquez, Ramón
,
Estrada Mena, Francisco Javier
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized countries. It is estimated that AMD affects at least 1 in 10 Hispanics. Previous reports have shown that AMD has multiple risk factors. Recently, we demonstrated that some genetic variants in the SGCD gene are involved in AMD developments, especially in early-stage (geographic atrophy, GA). Therefore, to evaluate the relationship between SGCD's absence and the loss of photoreceptors in GA, we worked with a genetically modified mouse model, SGCD deficient (Sgcd-/-) and a control mouse C57BL/6J (Sgcd+/+). First, we obtained hematoxylin and eosin (H&E) retina staining microscopic images. Then, we coarsely selected the outer and inner nuclear retinal layer (ONL and INL respectively) and finally, we applied an automatic nuclei segmentation to calculate the nuclear density in each region. Our results showed that Sgcd absence does not result in photoreceptor loss, on the contrary, it promotes an increment in nuclear density by 8.7% in ONL and 20.1% in INL compared with control eyes (p = 0.0033 and p < 0.0001 respectively). This could be explained by the fact that SGCD codifies the delta-sarcoglycan protein and there is evidence that showed a relationship between the absence of this protein with the activation of a cell proliferation signaling pathway. Finally, our results show that the delta-sarcoglycan protein could play an important role in the pathogenesis of the geographic atrophy. Moreover, there are promising perspectives for the systematic approach applied for cell image analysis, as an important tool to determine the nuclear density for assessing the progression of AMD. ©COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.