Research

Role of elevated intracranial pressure in SANS
(Supported by the Mississippi Space Grant Consortium)

Spaceflight-Associated Neuro-ocular Syndrome (SANS) emerges as a fascinating yet challenging phenomenon encountered by astronauts during prolonged space missions, especially those enduring months aboard the International Space Station. At the core of SANS lies the intricate interplay of physiological factors, with elevated intracranial pressure standing out as a pivotal risk element. The complexities surrounding this condition demand a more nuanced exploration to unravel the mysteries of its origins and impact on visual health.

In this project, we aim to comprehensively characterize the biomechanical and hemodynamic environment within the optic nerve head under elevated intracranial pressure. Through a combined experimental and computational approach, our goal is to elucidate the underlying mechanisms contributing to vision impairment observed in astronauts following long-duration missions. 

Effects of intraocular and intracranial pressures on glaucoma

Glaucoma stands as a leading cause of blindness worldwide, marked by the progressive degeneration of retinal ganglion cells and their axons. The onset of retinal ganglion cell axon damage in glaucoma is believed to occur at the optic nerve head, situated at the posterior of the eye. This crucial area is influenced by both intraocular pressure (IOP) from the eye and intracranial pressure (ICP) from the brain. Maintaining a delicate balance between the two pressures is essential for preserving the structural integrity and functionality of the optic nerve head. Disruptions in this equilibrium can lead to optic nerve damage and subsequent vision loss, characteristic features of glaucoma.

In this project, we aim to explore the interplay between IOP and ICP and their effects on the biomechanical and hemodynamic environment within the optic nerve head. Our goal is to elucidate the mechanisms of retinal ganglion cell axon damage in glaucoma, facilitating the development of novel treatments to prevent associated vision loss.

Myopia-induced changes in optic nerve head biomechanics

Myopia, commonly referred to as nearsightedness, represents a prevalent vision disorder characterized by difficulties in visualizing objects at a distance. However, its implications extend beyond mere visual impairment, as the elongation of the myopic eye poses significant risks for the development of severe ocular pathologies, notably glaucoma. This complex interplay between myopia and glaucoma underscores the pressing need for a deeper understanding of their underlying mechanisms and potential therapeutic avenues.

In this project, we aim to investigate how eye elongation in myopic eyes affects the biomechanical and hemodynamic environment within the optic nerve head. Our ultimate goal is to uncover the underlying mechanisms of the association between myopia and glaucoma. By understanding these mechanisms, we can potentially identify new therapeutic targets for the prevention and treatment of glaucoma in individuals with myopia. 

Biomechanics in blast-related ocular trauma

Ocular trauma, particularly resulting from blast injuries, has emerged as a significant concern within military combat contexts. Despite advancements in protective gear and medical interventions, it remains a prevalent threat to soldiers' visual health. Shockingly, recent statistics underscore the gravity of the issue. In a comprehensive analysis of 387 soldiers injured during Operation Iraqi Freedom, ocular trauma ranked as the fourth most common injury sustained, with a staggering 89% of these soldiers experiencing ocular injuries. Such high prevalence underscores the urgent need for innovative approaches to understand and mitigate the impact of blast-related ocular trauma.

In this project, we aim to develop an experimentally validated computational model of the eye to study the mechanics of blast wave-eye interactions. Understanding the loading mechanics of eye tissues is crucial for comprehending the pathophysiology of blast-related ocular trauma and designing effective blast wave mitigation strategies.

Factors influencing blood flow and oxygenation in the lamina cribrosa

We aimed to identify factors influencing minimum oxygen levels in the lamina cribrosa (LC), indicating heightened hypoxia risk. Unable to directly measure LC hemodynamics, we created 3D LC vasculature models using post-mortem monkey eye vasculature. Monte Carlo sampling generated 200 models, with varying vessel parameters and pressures. ANOVA revealed vessel diameter, neural tissue oxygen consumption rate, and arteriole pressure as key influencers. There was a strong interaction between vessel diameter and arteriole pressure whereby the impact of one factor was larger when the other factor was small.

Related Publications:

1. *Hua, Y., *Lu, Y., *Walker, J., Lee, P.Y., Tian, Q., McDonald, H., Pallares, P., Ji, F., Brazile, B.L., Yang, B. and Voorhees, A.P., 2022. Eye-specific 3D modeling of factors influencing oxygen concentration in the lamina cribrosa. Experimental Eye Research, 220, p.109105. [Link]
   (* Authors contributed equally to the manuscript)

2. Lee, P.Y., Hua, Y., Brazile, B.L., Yang, B., Wang, L. and Sigal, I.A., 2022. A workflow for three-dimensional reconstruction and quantification of the monkey optic nerve head vascular network. Journal of Biomechanical Engineering, 144(6), p.061006. [Link]

3. Waxman, S., Brazile, B.L., Yang, B., Lee, P.Y., Hua, Y., Gogola, A.L., Lam, P., Voorhees, A.P., Rizzo III, J.F., Jakobs, T.C. and Sigal, I.A., 2022. Lamina cribrosa vessel and collagen beam networks are distinct. Experimental Eye Research, 215, p.108916. [Link]

4. Brazile, B.L., Yang, B., Waxman, S., Lam, P., Voorhees, A.P., Hua, Y., Loewen, R.T., Loewen, N.A., Rizzo, J.F., Jakobs, T. and Sigal, I.A., 2020. Lamina cribrosa capillaries straighten as intraocular pressure increases. Investigative Ophthalmology & Visual Science, 61(12), pp.2-2. [Link]

Role of radially aligned scleral collagen fibers in optic nerve head biomechanics

The radial fibers within the peripapillary sclera, along with circumferential ones, play a crucial role in providing biomechanical support to the optic nerve head (ONH). Through finite element modeling, we investigated their impact on scleral canal biomechanics under varying intraocular pressure (IOP) conditions. Our findings reveal that radial fibers mitigate posterior lamina displacement, reduce radial strain in the peripapillary sclera and retinal tissue, and maintain strains within the ONH comparable to circumferential fibers alone. Combining both fiber types offers superior protection against excessive IOP-induced deformation, emphasizing their complementary roles in supporting the ONH.

Related Publications:

1. Hua, Y., Voorhees, A.P., Jan, N.J., Wang, B., Waxman, S., Schuman, J.S. and Sigal, I.A., 2020. Role of radially aligned scleral collagen fibers in optic nerve head biomechanics. Experimental Eye Research, 199, p.108188. [Link]

2. Gogola, A., Jan, N.J., Lathrop, K.L. and Sigal, I.A., 2018. Radial and circumferential collagen fibers are a feature of the peripapillary sclera of human, monkey, pig, cow, goat, and sheep. Investigative Ophthalmology & Visual Science, 59(12), pp.4763-4774. [Link]

3. Jan, N.J., Lathrop, K. and Sigal, I.A., 2017. Collagen architecture of the posterior pole: high-resolution wide field of view visualization and analysis using polarized light microscopy. Investigative Ophthalmology & Visual Science, 58(2), pp.735-744. [Link]

Influence of cerebrospinal fluid pressure on optic nerve head biomechanics

We aimed to understand how acute changes in intraocular pressure (IOP), cerebrospinal fluid pressure (CSFP), and central retinal artery blood pressure (BP) affect the biomechanics of the optic nerve head (ONH). Expanding a previous numerical model, we considered 24 factors and studied 8340 models. The six most influential factors were, in order: IOP, CON, moduli of the sclera, lamina cribrosa (LC) and dura, and CSFP. IOP and CSFP affected different aspects of ONH biomechanics. The strongest influence of CSFP, more than twice that of IOP, was on the rotation of the peripapillary sclera. CSFP had a similar influence on LC stretch and compression to moduli of sclera and LC. On some ONHs, CSFP caused large retrolamina deformations and subarachnoid expansion. CON had a strong influence on LC displacement. BP overall influence was 633 times smaller than that of IOP.

Related Publications:

1. Hua, Y., Voorhees, A.P. and Sigal, I.A., 2018. Cerebrospinal fluid pressure: Revisiting factors influencing optic nerve head biomechanics. Investigative Ophthalmology & Visual Science, 59(1), pp.154-165. [Link]

2. Hua, Y., Tong, J., Ghate, D., Kedar, S. and Gu, L., 2017. Intracranial pressure influences the behavior of the optic nerve head. Journal of Biomechanical Engineering, 139(3), p.031003. [Link]