Age-Related Loss of Human Vitreal Viscoelasticity

Abstract

Purpose To determine the viscoelasticity of human vitreous bodies and its changes with age in order to benefit the understanding and therapy of vitreoretinal diseases. Methods In a postmortem study, 190 human vitreous bodies were extracted from 33- to 92-year-old donors, analyzed with regard to their viscoelastic properties via dynamic mechanical analyses, and compared with bovine and porcine vitreous. Postmortem intervals and donor-related parameters were examined as potential parameters influencing vitreous viscoelasticity. Dynamic moduli of different hyaluronic acid (HA) solutions as well as human vitreous treated with HA injections were determined by frequency sweep tests. Results With age the viscoelasticity of human vitreous bodies decreased significantly and independently of postmortem intervals, diabetes, and the donor's sex. The storage modulus G′ and loss modulus G″ correlated strongly with the donor's age with r = −0.789 and r = −0.764, respectively. Bovine and porcine vitreous bodies exhibited dynamic moduli comparable only to the viscoelastic properties of aged human vitreous and are thus limited models for the simulation of the human vitreous. The viscoelasticity of aged human vitreous bodies was found to be increased after intravitreal injections of highly concentrated HA. Conclusions The present postmortem study is the first to show a significant age-related reduction in the viscoelasticity of entire human vitreous bodies. Highly concentrated HA injections may serve as a possible therapeutic approach for restoring the viscoelasticity of aged vitreous bodies. Translational Relevance These findings improve the understanding and therapy of the vitreous liquefaction with age and the associated vitreoretinal diseases.

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

“…However, stiff hydrogels can be difficult to inject through a small gauge needle into the vitreous chamber. The storage and loss moduli of synthetic hydrogels 34,[59][60][61][62]69,73,74,76,[81][82][83] (G' = 1203 ± 755 Pa, n = 18 and G" = 373 ± 330 Pa, n = 12) and semisynthetic hydrogels [92][93][94]97,98,[100][101][102]104 (G' = 1330 ± 1090 Pa, n = 9 and G" = 291 ± 223 Pa, n = 9) are approximately two orders of magnitude higher, while natural hydrogels' 37,110 (G' = 99.4 ± 53.4 Pa, n = 3 and G" = 51.5 ± 48.5 Pa, n = 2) are about one order of magnitude higher compared to the human vitreous [15][16][17] (G' = 5.09 ± 1.86 Pa, n = 3 and G" = 1.81 ± 0.98 Pa, n = 3). Hydrogels with different mechanisms of injection into the eye also have a wide variation in storage and loss moduli ( Table 5 and Figure 4B).…”

“…30 The assumptions used in their analytical model (homogeneous and spherical vitreous), limited image resolution, and patient compliance might explain the high standard deviation (300 ± 100 Pa) and drastic difference from the moduli directly measured using shear rheology on in vitro dissected vitreous samples reported by other studies. [15][16][17] However, to the best of the authors' knowledge, Piccirelli et al (2012) is the first study that reported the in vivo storage and loss moduli of the human vitreous humor. It is likely that the measured moduli from in vitro and ex vivo experiments are slightly lower than in vivo due to tissue degradation and destruction of the tissue architecture during testing.…”

A Hydrogel Vitreous Substitute that Releases Antioxidant

“…Rheological experiments showed viscoelastic properties of the PEGDA and PEGDA‐ co ‐PEGMA hydrogels similar to the native tissue . The linear viscoelastic region for both hydrogels was determined to be below 10% strain ( Figure 3 A).…”

“…The storage modulus ( G ′) and loss modulus ( G ″) of both hydrogels were in the same order of magnitude as the natural human vitreous (Figure 3B). The storage modulus of the human vitreous ranges from 1 to 7 Pa, whereas its loss modulus ranges from 0.3 to 1 Pa . The storage and loss moduli of the PEGDA hydrogel were statistically larger than those of the natural human vitreous with the storage modulus ranging from 5 to 11 Pa and the loss modulus averaging 0.9 Pa.…”

“…The PEGDA and PEGDA‐ co ‐PEGMA hydrogels have the most similar viscoelastic properties to those of the human vitreous humor, compared to previous studies (Table ). While the PEGDA‐ co ‐PEGMA hydrogel appeared to match the modulus of the human vitreous better than the PEGDA hydrogel, it should be noted that the reported properties of the human vitreous were dissected from older donors . It was suggested that the modulus of the in vivo vitreous might be higher compared to the dissected vitreous .…”