Salvatore Daniele

Selective binding of the epidermal growth factor and its specific effects on the epithelial cells of the cornea.

Abstract A selective binding of 131 I-labeled bioactive epidermal growth factor to rat epidermis and, especially, to the corneal epithelium has been reported. As far as the binding to the corneal epithelial cells is concerned no biochemical and/or metabolic modifications induced by the factor have been demonstrated so far. In the present work the following results have been obtained: 1. (1) The binding in vivo of the epidermal growth factor to the rat corneal epithelium is specific, since the affinity of the receptor cells for this factor is the highest ever found for all other tissues, including epidermis. 2. (2) The cells of adult rabbit corneal epithelium are very sensitive to the metabolic effects of the epidermal growth factor, as demonstrated by the stimulation induced by the factor on the uptakes of DNA, RNA, and, especially, labeled protein precursor in vitro. 3. (3) The epidermal growth factor is able to stimulate in vivo cell-proliferation of the adult rabbits corneal epithelium to a great extent. 4. (4) The epithelium healing process of simple non-perforating wounds in the corneas treated with the factor proceeds via the formation of a multilayer rather than as in the naturally occurring mechanism via a cellular monolayer. This suggests that the healing process is not only accelerated but that a somewhat different mechanism is triggered by the presence of the epidermal growth factor.

The effect of the epidermal growth factor (EGF) on the corneal epithelium in humans.

Epidermal growth factor (EGF) is a polypeptide hormone present in mammalian organs. In vivo, it shortens the time course of the corneal reepithelialization by stimulating a marked cell proliferation of the corneal epithelium. A further direct effect in vivo has been confirmed on human corneal epithelium and epidermis in culture. Tests in several nondystrophic diseases of the corneal epithelium confirmed the observations previously made in the rabbit that EGF accelerates the process of epithelial healing. The integrity of the corneal stroma is prejudicial for the maximum effect of the EGF, in the sense that the deeper the stroma is damaged, the less EGF acts. In herpetic lesions EGF is effective within 48 h only when the virusaffected area of the corneal epithelium has been scraped off. EGF is proposed as a new and efficacious agent for increasing the restorative process of the corneal epithelium in many nondystrophic diseases.

Treatment of persistent epithelial defects in neurotrophic keratitis with epidermal growth factor: a preliminary open study.

We report three patients with persistent epithelial defects in the context of neurotrophic keratopathy that healed while on treatment with topically applied, mouse-derived epidermal growth factor (m-EGF). The clinical course of these patients was striking and suggests that EGF may have a potential role in the treatment of persistent epithelial defects in subjects suffering from neurotrophic keratitis.

Progressive External Ophthalmoplegia Associated with Retinal Pigment Epitheliopathy

The diagnosis of ocular myopathy associated with a primary retinal pigment epitheliopathy in a 20-year-old man was based on the integrity of the retinal functions, despite progressive worsening of muscular activity in the systems affected by the disease, and on the results of retinal fluorescein angiography. Although the changes in the pigment epithelium were not prominent ophthalmoscopically, they were clearly visible angiograpically. Atypical forms of retinal pigment dystrophy occurring during the course of ocular myopathy appear to be clinical expressions of a unique genetic defect confined to the pigment epithelial layer. We assume that the gene is capable of inducing a pleiotropic effect.

Fundus Abnormalities in Cushing's Disease: A Preliminary Report

Three patients, 2 males and 1 female, with intrasellar, hypersecretive pituitary adenoma were studied. Blood hypertension was present in all and hyperglycemia in 2 (1 male, 1 female). None had neurological signs of compression of the optic disk or chiasma. One patient showed bilateral circumpapillary and multiple retinal pigment epithelium (RPE) detachment with pooling defects and intraretinal leakage from small retinal arterioles. Another had loss of foveolar, macular and retinal reflexes in the right eye; negligible RPE changes became visible with fluorescein angiography. The third, who had developed malignant hypertension, manifested bilateral hypertensive neuroretinopathy and papilledema. The simultaneous improvement of general and ocular symptoms after removal of the pituitary tumor makes a causal relationship possible and even very likely, between the underlying disorder and fundus abnormalities.

Congenital ocular and other systemic abnormalities associated with ring-11 chromosome

The ocular and systemic abnormalities in a boy with ring chromosome 11 [46, XY/46, XY, r(11) (p 15.5 → q25] are described. The ocular anomalies consisted of bilateral hypermetropia, microcornea, anterior chamber cleavage syndrome with prominent Wolfflin nodes, and cartwheel configuration of the anterior iris leaf. The systemic changes consisted of skeletal, muscular and articular defects, obesity, cryptorchidism, and mild mental retardation.

Progression of Choroidal Atrophy in Acute Posterior Multifocal Placoid Pigment Epitheliopathy

Acute posterior multifocal placoid pigment epitheliopathy is a non-granulomatous chorioretinitis of uncertain origin that occurs in healthy young adults. The prevailing opinion is that the disease has a good long-term prognosis for visual acuity because it is self-limiting and chorioretinal scars do not enlarge with time. A middle-aged adult male who had acute posterior multifocal placoid pigment epitheliopathy in one eye has been followed for 22 years. After apparent clinical healing of the placoid epithelial lesions, widespread severe choroidal atrophy with visual loss occurred and progressed over years without interruption. To our knowledge this is the second report of progressive deterioration of a supposedly self-limiting chorioretinal disease.

Analysis of the rhodopsin and peripherin/RDS gene in two families with pattern dystrophy of the retinal pigment epithelium

Mutations of the peripherin/retinal degeneration slow (RDS) gene have been reported in autosomal dominant retinitis pigmentosa and variable forms of pattern dystrophy of the retinal pigment epithelium. We screened the rhodopsin and the peripherin/RDS gene in the members of two families who presented the clinical features of pattern dystrophy of the retinal pigment epithelium transmitted as an autosomal dominant trait. No migration patterns were detected in single strand conformation polymorphism or hydrolink gels. Both the rhodopsin and the peripherin/RDS gene were normal in one family. In the second, the proband had a normal rhodopsin gene and, although he passed a different haplotype to each of his affected daughters, there was no linkage with the peripherin/RDS gene. The origin of the retinal disturbance in our two pedigrees must therefore be sought, if indeed DNA is involved, elsewhere in the genome. Our findings provide additional evidence that pattern dystrophies of the retinal pigment epithelium may be pathogenically related in spite of different etiological origins. The genetic polymorphism can probably account for the wide range of phenotypes.

Association of peripapillary scars with lesions characteristic of multiple evanescent white-dot syndrome

Multiple evanescent white-dot syndrome, acute idiopathic blind-spot enlargement syndrome and multifocal choroiditis (pseudo-ocular histoplasmosis syndrome) are fundus diseases of unknown etiology. A single etiological agent or group of similar agents is thought to be responsible for these relatively rare manifestations. A 35-year-old male with associated symptoms of enlargement of the blind spot, evanescent white-dot syndrome and presumed ocular histoplasmosis is described. The association of these highly differentiated fundus abnormalities strengthens the hypothesis of an etiological or pathological linkage within phenotypically variable clinical forms.

Influence of the vitreous body on the lens proteins

When a dialyzate of the vitreous body is added to whole lens extracts in vitro, a confluence of the α and β fractions is observed in the electrophoretic pattern. This property of the vitreous body increases with age. This effect also depends on the concentration of the α fraction in the lens extract, viz. the less the α-crystallin content, the more prominent the electrophoretic confluence produced by the vitreous body of the same eye. The vitreous body contains dialyzable compounds which oxidize the SH groups of added cysteine and cause a marked increase in the reactivity of the protein-SH groups of the lens homogenate. Like the first property, these also increase with age, but they seem to originate from different factors.