Balder P. Gloor

Vitreoretinal juncture; healing of experimental wounds

Healing of mechanically-induced, minimal wounds of vitreoretinal juncture in non-vascularized retina of rabbits was studied with electron microscopy at 1 and 3 days, and 1, 2, 6 and 10 weeks. Neuroectodermal scar was formed by two processes, each having a specific anatomical relationship to wound. Accessory gliocytosis, in which accessory glia adjacent to wound become phagocytic and proliferate; following this their progeny migrate to wound and progressively differentiate into fibrous astrocytes to fill in the wound proper. Plexiform gliosis, in which the Müller cell side branches proliferate to form a layer about the perimeter of wound. The retinal inner limiting lamina did not regenerate. The significance of these findings in relation to epiretinal membrane formation in man is discussed. Die Heilung mikrochirurgisch gesetzter mechanischer Wunden im Bereich der vitreoretinalen Grenzschicht der nicht vaskularisierten Kaninchennetzhaut wurde 1 und 3 Tage, 1, 2, 6 und 10 Wochen nach Setzen der Laesion elektronenmikroskopisch untersucht. Die neuroektodermale Narbe wird im wesentlichen durch 2 Prozesse gebildet, wobei jeder seine spezielle anatomische Relation zur Wunde hat: Der erste besteht in einer akzessorischen Gliozytose. Dabei entwickeln am Wundrand akzessorische Gliazellen eine phagozytotische Aktivität und proliferieren. Solche undifferenzierte Gliazellen wandern in die Wunde und differenzieren in fibröse Astrocyten und füllen die eigentliche Wunde aus. Der zweite besteht in einer plexiformen Gliose, bei welcher Protoplasma-Verzweigungen der Müllerschen Stützzellen proliferieren und eine Schicht in der Wundumgebung bilden. Nicht neu geformt wird die Lamina limitans interna. Die Bedeutung dieser Befunde für die Bildung epiretinaler Membranen beim Menschen wird diskutiert.

On the question of the origin of macrophages in the retina and the vitreous following photocoagulation (autoradiographic investigations by means of 3H-thymidine)

The question of the origin of the macrophages in the retina and in the vitreous following photocoagulation was investigated in fourteen albino rabbits by means of 3H-thymidine. A group of seven animals were photocoagulated, the others served as controls. Prior to photocoagulation all fourteen rabbits received intravenous injections of 3H-thymidine three times at intervals of twelve hours to label all hematogenous macrophages then being formed in the bone marrow. Cells of the pigment epithelium and of the neurosensory retina on the other hand, normally being in the Go-phase, remain unlabeled. The animals were sacrificed at one hour, 24 hours and thereafter at daily intervals till the sixth day following photocoagulation. Five hours before death they received colchicine. In this way one was able to determine, wether previously labeled cells of the bone marrow undergo further mitosis following release into the tissues. Twentysix hours following photocoagulation one finds in photocoagulated animals numerous labeled cells in the area of the lesion at the walls of choroidal vessels, further immediately inside Bruchs membrane in between the photoreceptors, later even in the inner retinal layers and the adjoining vitreous, contrasting with the findings in the controls. In the ciliary region in both groups labeled cells occur in the stroma, between the epithelial cells and in the vitreous. These labeled cells in the coagulated animals increase with time more than in the controls. Numerous such labeled cells are arrested in metaphase by the colchicine. Our experiments show that at least the greater part of the macrophages appearing in and about retinal lesions following photocoagulation are of hematogenous origin. Continual immigration of hematogenous macrophages through the ciliary region, which is increased following photocoagulation, also seems most likely to take place, though this is not completely proven by this study. Die Frage der Herkunft der Makrophagen in der Retina und im Glaskörper nach Lichtkoagulation wurde bei 14 Albino-Kaninchen untersucht. 7 Tiere wurden photokoaguliert, die andern dienten als Kontrolle. Vor der Photokoagulation erhielten alle 14 Kaninchen 3mal in 12stündigen Intervallen 3H-Thymidin i.v. injiziert, um die im Knochenmark entstehenden hämatogenen Makrophagen zu markieren. Andererseits bleiben Pigmentepithel und Netzhautzellen, weil sie sich normalerweise in einer Go-Phase befinden, nicht markiert. Die Tiere wurden 1 Std, 24 Std und darauf bis zum 6. Tag in täglichen Intervallen nach der Photokoagulation getötet, 5 Std vor dem Tod erhielten sie Colchicine. Damit kann festgestellt werden, ob vorher markierte Knochenmarkszellen nach Ausschwemmung ins Gewebe weiter proliferieren. 26 Std nach Lichtkoagulation finden sich bei den koagulierten Tieren im Bereiche der Läsion an den Wänden der Chorioideagefäße, dann aber auch unmittelbar innerhalb der Bruchschen Membran zwischen Photorezeptoren reichlich markierte Zellen, später auch bis in die innersten Schichten der Retina und des angrenzenden Glaskörpers, nicht aber in den Kontrolltieren. In der Ciliarregion finden sich sowohl in den koagulierten wie in den Kontrolltieren markierte Zellen im Stroma, zwischen den Epithelzellen und im Glaskörper. Diese markierten Zellen nehmen mit der Zeit im Glaskörper bei den koagulierten Tieren mehr als bei den Kontrolltieren zu. Zahlreiche dieser markierten Zellen liegen in Colchicine blockierter Metaphase vor. Die Versuche zeigen, daß mindestens ein großer Teil der nach Lichtkoagulation in und um die Läsion der Retina auftretenden Makrophagen hämatogenen Ursprungs sind. Eine dauernde Einwanderung von hämatogenen Makrophagen durch die Ciliarregion, welche nach Lichtkoagulation verstärkt ist, erscheint ebenfalls sehr wahrscheinlich, ist aber mit diesen Versuchen nicht strikte bewiesen.

Zur Entwicklung des Glaskörpers und der Zonula

The incorporation of 3H-labeled amino acids and 3H-labeled glucose into the zonule of the developing eye of mouse was investigated. The amino acids chosen were proline and glycine, which are usually present in large amounts in collagen, and lysine, methionine, and cystine, which are normally scarce or absent. The 3H-glucose was used as a precursor of glycosaminoglycans. In a first experiment with 380 mice aged 2–60 days, the fate of the labeled substances was investigated following a single i.p. injection. The animals were sacrificed at different intervals from 5 min to 8 days after the injection. In a second experiment (70 animals), the cumulation and the time of disappearance of the 3H-labeled amino acids and 3H-labeled glucose were investigated. The animals received injections every 12 hours. In a first series of investigations mice aged one day at the beginning were used, and in a second series mice aged 12 days. The animals were sacrificed after different periods of cumulation, the longest being 14 days. Five animals which received injections throughout the period of cumulation were sacrificed 1–21 days after the last injection. The experiments show that development of the zonula of mouse starts between the 4th and 7th days of life and ends about the 24th day. All the amino acids tested were incorporated into the zonule, especially cystine and methionine. This suggests that the zonular fibers are not made up of normal collagen; they may consists of some sort of a procollagen. The zonular fibers may be a basal membranelike component of the ciliary epithelium. The amounts of glucose used in this experiment were not large enough to allow detection of any incorppration into the zonular fibers. Es wurde der Einbau von radioaktiv markierten Aminosäuren und 3H-Glucose in die Zonula der Maus während der Entwicklung untersucht. Verwendet wurden einerseits 3H-Prolin und 3H-Glycin, weil diese Substanzen, normalerweise reichlich in Kollagen vorhanden sind, und andererseits 3H-Lysin. 3H-Methionin und 3H-Cystin, welche üblicherweise kaum oder gar nicht in Kollagen nachgewiesen werden können. 3H-Glucose wurde als Aminoglycan-Vorläufer benutzt. In einem ersten Experiment an 380 Albinomäusen wurde das Verhalten der Aminosäuren nach einer einzelnen intraperitonealen Injektion untersucht. Mäuse im Alter von 2–60 Tagen standen im Versuch. In einem zweiten Experiment wurde die Akkumulation und die Zeit des Verschwindens der 3H-markierten Substanzen überprüft. Die Tiere erhielten alle 12 Std repetierte Injektionen während mehreren Tagen. In einer ersten Serie begann das Experiment mit Mäusen im Alter von 1 Tag, in einem zweiten im Alter von 12 Tagen. Die Tiere wurden nach verschieden langen Akkumulationsperioden getötet, die längste betrug 14 Tage. Die Untersuchungen zeigen, daß in der Maus die Entwicklung der Zonula zwischen 4. und 7. Lebenstag beginnt und bis zum 24. Tag dauert. Alle verwendeten Aminosäuren werden in die Zonulafasern eingebaut, neben Prolin und Glycin insbesondere auch Cystin und Methionin. Dies spricht dafür, daß es sich bei den Zonulafasern nicht um übliches, reifes Kollagen, möglicherweise aber um ein Prokollagen handelt. Die Bildungsstätte könnte das Ciliarepithel sein, wobei es sich bei den Zonulafasern um eine basalmembranartige Bildung dieses Epithels handeln würde. Die verwendeten Mengen von Glucose waren zu niedrig, um einen Einbau in die Zonula nachweisen zu können.

Cell Cycle Time and Life-Span of Cells in the Mouse Eye

In this investigation the cell cycle time and the life-span of cells in different tissues of the mouse eye were determined during postfetal development not with single but, instead, by means of repeated 3H-thymidine injections. The potential of this method applied for the first time in the mammalian eye, is thoroughly discussed. Essentially, four groups of 19-21 mice each, aged 1, 10, 20, and 60 days at the start of the experiment, received intraperitoneal injections of 3H-thymidine at a dose of 1 microCi/g body weight every 4 h for a maximum of 14 days, i.e. a total of up to 85 injections. Further animals were sacrificed after the 13th, 19th, 25th, 31st, 37th, 49th, 61st, 73rd, and 85th injections, i.e. 2, 3, 4, 5, 6, 8, 10, 12, and 14 days after the start of the experiment. When all the injections had been given, animals from each group were sacrificed on the 1st, 4th, 8th, 16th, and sometimes the 32rd, 48th, and 64th days, respectively, after the last injection. With this experimental paradigm it was possible: (1) to determine the cell cycle time and the life-span of the cells during postfetal development up to maturity without gaps; (2) to establish the end of the development by means of cell proliferation in various tissues of the mouse eye; herewith it was possible to determine the times at which the development by cell proliferation is replaced by development by cell differentiation, and (3) to clearly prove in which mature ocular tissues cell turnover still exists and in which it does not; this appears to be especially important, since in recent years the importance of cell proliferation process following injury and stimulation was also recognized in the eye, for example, in massive periretinal proliferation in connection with retinal detachment and retinal surgery, as well as in endothelial injuries following intraocular lens implantation; only when normal conditions are known can pathological proliferative processes be recognized as such and be distinguished from normal ones. The results are cumulatively represented in tabular form, from which details are to be extracted. As expected, cell cycle times are very short and seemingly homogeneous in tissues which develop within themselves, but become longer and inhomogeneous, except in the inner and outer granular layer of the retina, in which the cell proliferation comes to a particularly abrupt end. The shortest cell cycle time occurred in the cells of the vascular walls of the retina at the time of birth and was 24 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Protracted ruthenium treatment of recurrent pterygium

By combining excision with 106ruthenium irradiation in 17 patients previously operated on for persistently recurrent pterygium; we have devised an effective therapy that produces virtually no side effects and further prevents events recurrence. The ruthenium applicator shell was left in place for 2–3 h, yielding a total dosage of 2000 cGy. Only 2 of 17 patients suffered even slight recurrences, and 2 more had either motility disturbance or corneal haze. Through application of the internationally accepted total dosage of 2000 cGy, but at a relatively low dose rate, which especially protects the tissue responsible for proper healing, strong support is provided for the principle of protracted irradiation in recurrent (and possibly even primary) pterygium, permitting milder treatment and fewer recurrences.

Why Jules Gonin Achieved His “Audacious Goal Initiative”—and Why He Is a Model for the Present Day

The journal Science gained national attention in March 2015 with a news feature on the winner of the National Eye Institute’s Audacious Goal Initiative competition. The National Eye Institute’s winning choice was “to regenerate neurons and neural connections in the eye and visual system.” The article, entitled “Second Sight: Eye Transplants Are Science Fiction. A Team of Researchers Wants to Change That,” implies this goal is within reach in the foreseeable future. Rolling back the calendar 100 years, we find in ophthalmology the achievement of another audacious goal. In the early 20th century, the foundations for the modern techniques of cataract surgery, corneal transplant surgery, and treatment of glaucoma and strabismus were in place already, but the idea that a detached retina could be reattached, made to stay in place, and resume its normal function was an audacious notion on a par with any Jules Verne

Franz Fankhauser: The Father of the Automated Perimeter

Franz Fankhauser is known as the father of automated perimetry and of the q-switched Nd:YAG laser knife. His 15-year journey to computerize perimetry started in 1958 with unsuccessful attempts to automate kinetic perimetry. The switch to using static perimetry resulted in a breakthrough in 1973, and in 1975 the OCTOPUS perimeter came on the market. At the same time Fankhauser was working on the use of light sources for the treatment of ocular tissues. During his career, Fankhauser worked in very close collaboration with mathematicians, physicists, engineers. One of the most astonishing characteristics of Fankhauser was his ability to find and to motivate young scientists to work as a cohesive group for his projects.

Alfred vogt (1879-1943).

Alfred Vogt (1879-1943) was one of three ophthalmologists from the German-speaking part of Switzerland who had an exceptional impact on ophthalmology during the 20th century; the other two were Hans Goldmann (1899-1991) and Franz Fankhauser (1924-). Vogt is known for his natural gift of observation, his extraordinary memory for facts, and an enormous working capacity. Unfortunately, Vogts merits and exceptional surgical skills were sometimes overshadowed by his aggressive nature.

Jules Gonin: Proving the Cause and Cure of Retinal Detachment

Jules Gonin (1870–1935) did not originate the concept that retinal holes are a cause of detachment, but he had the insight to recognize its verity at a time that few surgeons did. He also understood that to treat holes it first would be necessary to localize them. He had the drive and resources to gradually refine his techniques for recognizing and sealing retinal tears until the cumulative weight of his clinical success proved the point. He is justly famous as the man who made retinal detachment a treatable disease.

[Transport of 131J-iodo-o-hippurate and 22Na out of the retroretinal space in experimental non rhegmatogenous detachment of the retina (author's transl)].

A model of an experimental arhegmatogenous retinal detachment is presented, to allow the measurement of the transport of radioactive labeled substances out of the subretinal space. Experiments were performed on 19 male cats.131I-iodo-o-hippurate and22Na were used as test substances. There was no, significant difference between the rate of disappearance of131I-hippurate if injected retroretinally or intravitreally. The rate of disappearance of131I-hippurate could be slowed down by intravenous infusion of penicillin-G. The rate of disappearance of22Na following retroretinal injection is not only slower than the rate of disappearance of22Na injected intravitreally, but significantly slower than the rate of disapperance of131I-hippurate. For graphic analysis (“curve peeling”) of the terms embodied in the curves, more densly situated points of measurements will be necessary. Then the experimental model will serve well to analyze the components influencing the transport of labeled sodium out of the subretinal space. Es wird ein Modell einer experimentellen arhegmatogenen Amotio retinae vorgestellt, welches erlauben soll, den Abtransport radioaktiv markierter Substanzen aus dem Subretinalraum zu messen und mit demjenigen aus dem Glaskörper zu vergleichen. Im Versuch standen 19 Katzen. Verwendet wurden als Testsubstanzen131Jod-Hippuran und22Natrium. Es konnte kein signifikanter Unterschied zwischen der Abtransportgeschwindigkeit von131J-Hippuran aus dem subretinalen Raum und dem Glaskörper gefunden werden. Der Abtransport von Hippuran aus dem subretinalen Raum ist mit Penicillin hemmbar. Der Abtransport von22Na erfolgt signifikant langsamer als derjenige von131J-Hippuran. Für eine graphische Analyse der Abfallkurven und der in diesen enthaltenen exponentiellen Begriffe sind dichter liegende Meßpunkte notwendig. Das Versuchsmodell dürfte dann aber die Analyse der einzelnen Komponenten, welche den Natrium- und damit den Flüssigkeitstransport aus dem retroretinalen Raum beeinflussen, erlauben.