Browsing by Subject "Eye"

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    Formation Of Exogenic Pituitary, Eye Lens, And Midbrain Dopaminergic Neurons In Pigs Via Blastocyst Complementation
    (2016-12) Mikkila, Jennifer
    Thousands of patients die waiting for an organ transplant every year, while those that do obtain a transplant may run into complications such as Graft vs. Host disease. One reason for this is that there is a lack of organ donors who can biologically match specific patients. A solution to this problem would be to generate human organs in pigs using the patient’s own cells, and then to transplant these organs once they are grown. Blastocyst complementation is the perfect method to do this as it is involves injecting donor cells into a pig embryo, which can then contribute to growing to an organ in the pig if the pig’s own genetic code does not allow its own cells to form that very same tissue. Blastocyst complementation was previously done using PITX3 KO pig embryos and human induced pluripotent stem cells (hiPSCs) or human umbilical cord blood stem cells (hUCBSCs) in the Low Lab to create exogenic pituitaries, eye lenses, and midbrain dopaminergic neurons made of human cells. Human Nuclear Antigen staining of pituitaries in this study show positive signals. The human cells failed to integrate into the eye lens and midbrain dopamine neurons, despite the fact that the dopaminergic neurons were complemented and able to grow into functional cells. This failure could have been due to either incorrect stage-matching of donor cells to the host embryo, or knocking out a gene that was only partially responsible for cellular development. A second gene, LMX1A, was therefore knocked out together with PITX3 to try and get complementation with GFP-labelled porcine blastomeres. This study shows that the eye lenses of these embryos are similar in terms of a round, circular morphology to that of wild-type pig lenses. GFP is found to be present in the pituitary of a PITX3/LMX1A KO embryo injected with porcine blastomeres, meaning the donor cells successfully integrated into the organ.
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    Iris biomechanics in health and disease.
    (2010-05) Amini, Rouzbeh
    Computational models of the eye have been studied by various investigators. The main purpose of developing a computational model is to provide a better understanding of the normal function of the eye as well as the abnormalities causing ocular diseases. For instance, by using computational methods, new insights have been brought to the pathophysiology and anatomical risk factors of angle-closure glaucoma, a mysterious eye disease closely related to the mechanics of the iris. Unlike the clinical research, computational studies are neither hindered by experimental difficulties nor by patient health risks. We developed computational models of the ocular tissues at three different levels to understand the mechanisms by which ocular globe deformation, iris-aqueous-humor interaction, and detailed iris structure affect the iris configuration. These models include: a finite-element model of the whole ocular globe consisting of the iris, cornea, sclera, and limbus, a finite-element model of iris-aqueous-humor interaction in the anterior eye, and a finite element model of the iris with its active and passive constituent tissues. Our whole-globe simulation showed that corneoscleral indentation, a diagnostic and/or treatment method in various glaucoma-related complications, would lead to changes in the anterior chamber angle. Our model showed that the limbus, due to its unique mechanical properties, plays an important role in the deformation of the whole ocular globe. Simulations performed using our anterior-segment model showed that the rapid changes (~sec) in the iris-aqueous-humor system due to corneoscleral indentation may lead to long recovery times (~min). We showed that a similar long recovery mechanism prevents the iris from drifting forward during normal blinking. Finally, simulations based on the detailed iris anatomy showed that the posterior location of the dilator muscle could contribute to the iris anterior bowing following dilation even in the absence of the aqueous humor pressure difference. Clinical studies have emphasized the key role of the iris shape and configuration in physiology and pathophysiology of the eye. In the course of our research, we showed that iris configuration is ultimately affected by many parameters including deformation of the whole ocular globe, interaction with aqueous humor flow, and activation of its constituent muscles.